ethyl 7-isocyano-2,2-dimethyl-7-(4-methylphenyl)sulfonylheptanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2 H), 3.31 (br. s, 2 H), 2.42 (br., 1 H), 2.39 (m, 4 H), 1.54-1.48 (m, 6 H), 1.24-1.18 (m, 7 H), 1.14 (s, 6 μl), 0.86 (s, 6 H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H33O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6 μl), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2CO2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535. found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2CO2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2CO2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535. found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2CO2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2 H), 3.31 (br. s, 2 H), 2.42 (br., 1 H), 2.39 (m, 4 H), 1.54-1.48 (m, 6 H), 1.24-1.18 (m, 7 H), 1.14 (s, 6 μl), 0.86 (s, 6 H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H33O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6 μl), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2CO2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6H), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535. found: 315.2541. the internal temperature between 10 and 15° C The mixture was extracted with CH2Cl2 (3×15 mL) The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil extracted with CH2CO2 (3×15 mL) The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL) dried over anhydrous MgSO4 concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil