(3-iodophenyl) acetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Triisopropylsilanethiol (2.91 ml, 13.5 mmol) was added dropwise to a suspension of sodium hydride (325 mg, 13.5 mmol) in THF (10 ml). After the evolution of hydrogen ceased, a solution of 3-iodophenyl acetate (2.37 g, 9.0 mmol) and tetrakis(triphenylphosphine)palladium (0) (1.04 g, 0.9 mmol) in toluene (90 ml) was added. After refluxing for 16 h under argon, the reaction was cooled to room temperature and the solvent was evaporated under vacuum. The resulting residue was dissolved in ethyl acetate, washed with 1N NaOH and brine, dried with sodium sulfate, filtered, and evaporated under vacuum. The crude product was chomatrographed over silica gel to yield 1.53 g (52%) of 3-[1,1-bis (Methylethyl)-2-methyl-1-silapropylthio]phenyl acetate. NMR 1H Cl3CD δ: 7.34 (m, 2H), 7.23 (t, 1H, J=2.4 Hz), 6.94 (dd, 1H, J=1.2, 8.4 Hz), 2.28 (s, 3H), 1.25 (m, 3H), 1.08 (d, 18 H, J=7.2 Hz). After refluxing for 16 h under argon the solvent was evaporated under vacuum The resulting residue was dissolved in ethyl acetate washed with 1N NaOH and brine dried with sodium sulfate filtered evaporated under vacuum

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

Procedure: A solution of 3-iodophenol (3 g, 13.6 mmol), acetyl chloride (2.9 ml, 40.9 mmol) and potassium carbonate (9.42 g, 68.2 mmol) in N,N-dimethylformamide (75 ml) was stirred for 16 h at room temperature. The mixture was partitioned between water and ethyl acetate. The organic layer was washed with 1N NaOH, dried over magnesium sulfate, and evaporated under vacuum. The crude product was chromatographed over silica gel, eluting with 20% ethyl acetate/hexanes to yield 2.3 g (65%) of 3-iodophenyl acetate. The mixture was partitioned between water and ethyl acetate The organic layer was washed with 1N NaOH dried over magnesium sulfate evaporated under vacuum The crude product was chromatographed over silica gel eluting with 20% ethyl acetate/hexanes

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

Procedure: A solution of 3-iodophenol (3 g, 13.6 mmol), acetyl chloride (2.9 ml, 40.9 mmol) and potassium carbonate (9.42 g, 68.2 mmol) in N,N-dimethylformamide (75 ml) was stirred for 16 h at room temperature. The mixture was partitioned between water and ethyl acetate. The organic layer was washed with 1N NaOH, dried over magnesium sulfate, and evaporated under vacuum. The crude product was chromatographed over silica gel, eluting with 20% ethyl acetate/hexanes to yield 2.3 g (65%) of 3-iodophenyl acetate. The mixture was partitioned between water and ethyl acetate The organic layer was washed with 1N NaOH dried over magnesium sulfate evaporated under vacuum The crude product was chromatographed over silica gel eluting with 20% ethyl acetate/hexanes

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

Procedure: A solution of 3-iodophenyl acetate (5.6 g) (J. Org. Chem. 1983, 48,1542-4) in acetonitrile (100 mL) was treated with (Ph3P)2PdCl2 (673 mg) and Cul (368 mg) and stirred at room temperature. 3-Butyn-1-ol (1.78 g) was added and the reaction mixture stirred for a further 20 h and concentrated in vacuo. The residue was purified by chromatography (SPE, gradient from cyclohexane to DCM) to give the title compound. LCMS RT=2.54 min the reaction mixture stirred for a further 20 h concentrated in vacuo The residue was purified by chromatography (SPE, gradient from cyclohexane to DCM)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-(allyl-methanesulfonyl-amino)-heptanoic acid ethyl ester (250 mg, 0.86 mmol), 1-acetyloxy-3-iodo-benzene (225 mg, 0.86 mmol), and triethylamine (139 mL, 1 mmol) in DMF (3 mL) was added palladium acetate (25 mg). The reaction was heated to 80° C. under nitrogen for 24 h. The mixture was cooled to room temperature and aqueous sodium thiosulfate and CH2Cl2 were added. The aqueous solution was extracted with CH2Cl2 (2×) and the combined organic layers were washed with water (1×) and brine (1×). The organic solution was dried with MgSO4, filtered, and concentrated in vacuo. The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes) to afford the title compound of Step A (95 mg). 1H NMR (CDCl3 400 MHz) δ 6.88–7.34 (m, 4H), 6.53–6.60 (m, 1H), 6.13–6.20 (m, 1H), 4.10 (q, 2H), 3.95 (d, 2H), 3.17–3.21 (m, 2H), 2.85 (s, 3H), 2.24–2.31 (m, 2H), 2.31 (s, 3H), 1.56–1.62 (m, 4H), 1.27–1.33 (m, 4H), 1.23 (t, 3H). The mixture was cooled to room temperature The aqueous solution was extracted with CH2Cl2 (2×) the combined organic layers were washed with water (1×) and brine (1×) The organic solution was dried with MgSO4 filtered concentrated in vacuo The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-(allyl-methanesulfonyl-amino)-heptanoic acid ethyl ester (250 mg, 0.86 mmol), 1-acetyloxy-3-iodo-benzene (225 mg, 0.86 mmol), and triethylamine (139 mL, 1 mmol) in DMF (3 mL) was added palladium acetate (25 mg). The reaction was heated to 80° C. under nitrogen for 24 h. The mixture was cooled to room temperature and aqueous sodium thiosulfate and CH2Cl2 were added. The aqueous solution was extracted with CH2Cl2 (2×) and the combined organic layers were washed with water (1×) and brine (1×). The organic solution was dried with MgSO4, filtered, and concentrated in vacuo. The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes) to afford the title compound of Step A (95 mg). 1H NMR (CDCl3 400 MHz) δ 6.88–7.34 (m, 4H), 6.53–6.60 (m, 1H), 6.13–6.20 (m, 1H), 4.10 (q, 2H), 3.95 (d, 2H), 3.17–3.21 (m, 2H), 2.85 (s, 3H), 2.24–2.31 (m, 2H), 2.31 (s, 3H), 1.56–1.62 (m, 4H), 1.27–1.33 (m, 4H), 1.23 (t, 3H). The mixture was cooled to room temperature The aqueous solution was extracted with CH2Cl2 (2×) the combined organic layers were washed with water (1×) and brine (1×) The organic solution was dried with MgSO4 filtered concentrated in vacuo The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-(allyl-methanesulfonyl-amino)-heptanoic acid ethyl ester (250 mg, 0.86 mmol), 1-acetyloxy-3-iodo-benzene (225 mg, 0.86 mmol), and triethylamine (139 mL, 1 mmol) in DMF (3 mL) was added palladium acetate (25 mg). The reaction was heated to 80° C. under nitrogen for 24 h. The mixture was cooled to room temperature and aqueous sodium thiosulfate and CH2Cl2 were added. The aqueous solution was extracted with CH2Cl2 (2×) and the combined organic layers were washed with water (1×) and brine (1×). The organic solution was dried with MgSO4, filtered, and concentrated in vacuo. The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes) to afford the title compound of Step A (95 mg). 1H NMR (CDCl3 400 MHz) δ 6.88-7.34 (m, 4H), 6.53-6.60 (m, 1H), 6.13-6.20 (m, 1H), 4.10 (q, 2H), 3.95 (d, 2H), 3.17-3.21 (m, 2H), 2.85 (s, 3H), 2.24-2.31 (m, 2H), 2.31 (s, 3H), 1.56-1.62 (m, 4H), 1.27-1.33 (m, 4H), 1.23 (t, 3H). The mixture was cooled to room temperature The aqueous solution was extracted with CH2Cl2 (2×) the combined organic layers were washed with water (1×) and brine (1×) The organic solution was dried with MgSO4 filtered concentrated in vacuo The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-(allyl-methanesulfonyl-amino)-heptanoic acid ethyl ester (250 mg, 0.86 mmol), 1-acetyloxy-3-iodo-benzene (225 mg, 0.86 mmol), and triethylamine (139 mL, 1 mmol) in DMF (3 mL) was added palladium acetate (25 mg). The reaction was heated to 80° C. under nitrogen for 24 h. The mixture was cooled to room temperature and aqueous sodium thiosulfate and CH2Cl2 were added. The aqueous solution was extracted with CH2Cl2 (2×) and the combined organic layers were washed with water (1×) and brine (1×). The organic solution was dried with MgSO4, filtered, and concentrated in vacuo. The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes) to afford the title compound of Step A (95 mg). 1H NMR (CDCl3 400 MHz) δ 6.88-7.34 (m, 4H), 6.53-6.60 (m, 1H), 6.13-6.20 (m, 1H), 4.10 (q, 2H), 3.95 (d, 2H), 3.17-3.21 (m, 2H), 2.85 (s, 3H), 2.24-2.31 (m, 2H), 2.31 (s, 3H), 1.56-1.62 (m, 4H), 1.27-1.33 (m, 4H), 1.23 (t, 3H). The mixture was cooled to room temperature The aqueous solution was extracted with CH2Cl2 (2×) the combined organic layers were washed with water (1×) and brine (1×) The organic solution was dried with MgSO4 filtered concentrated in vacuo The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-(allyl-methanesulfonyl-amino)-heptanoic acid ethyl ester (250 mg, 0.86 mmol), 1-acetyloxy-3-iodo-benzene (225 mg, 0.86 mmol), and triethylamine (139 mL, 1 mmol) in DMF (3 mL) was added palladium acetate (25 mg). The reaction was heated to 80° C. under nitrogen for 24 h. The mixture was cooled to room temperature and aqueous sodium thiosulfate and CH2Cl2 were added. The aqueous solution was extracted with CH2Cl2 (2×) and the combined organic layers were washed with water (1×) and brine (1×). The organic solution was dried with MgSO4, filtered, and concentrated in vacuo. The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes) to afford the title compound of Step A (95 mg). 1H NMR (CDCl3 400 MHz) δ 6.88-7.34 (m, 4H), 6.53-6.60 (m, 1H), 6.13-6.20 (m, 1H), 4.10 (q, 2H), 3.95 (d, 2H), 3.17-3.21 (m, 2H), 2.85 (s, 3H), 2.24-2.31 (m, 2H), 2.31 (s, 3H), 1.56-1.62 (m, 4H), 1.27-1.33 (m, 4H), 1.23 (t, 3H). The mixture was cooled to room temperature The aqueous solution was extracted with CH2Cl2 (2×) the combined organic layers were washed with water (1×) and brine (1×) The organic solution was dried with MgSO4 filtered concentrated in vacuo The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes)