tert-butyl-(5-chloropentoxy)-dimethylsilane

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

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

Procedure: A mixture of t-butyldimethylsilyl chloride (29.5 g, 0.196 mole) and 5-chloro-1-pentanol (20 g, 0.163 mole) under an inert atmosphere was treated with a solution of imidazole (27.7 g, 0.407 mole) in dry DMF (40 mL). The reaction was stirred overnight at room temperature then partitioned between water (200 mL) and OEt2 l (300 mL). The aqueous layer was extracted with more OEt2 (2×100 mL), and the combined extract was dried (Na2SO4). The OEt2 was removed and the residue fractionally distilled. A small fore-run was collected (bp 57° C. (16 mm)) and then [(5-chloro-1-pentyl)oxy](1,1-dimethylethyl)dimethylsilane as a colorless oil (44.8 g, 97%): bp 120°-5° C. (17 mm), IR (film) cm-1 2960, 2940, 2900, 2865, 1475, 1465, 1390, 1365, 1290, 1260, 1110, 1055, 1030, 1010, 982, 940, 910, 840, 815, 780, 725, 660; 1H NMR (200 MHz, CDCl3) δ 3.62 (t, 6.1 Hz, 2H), 3.54 (t, 6.7 Hz, 2H), 1.79 (pentet, 7 Hz, 2H), 1.52 (m, 4H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (22.5 MHz, CDCl3) δ 62.8, 44.9, 32.5, 32.1, 26.0 (3C), 23.3, 18.3 (tertiary), -5.3 (2C); mass spectrum (70 eV) m/e (% base) 238, 236 (M+, not observed), 181, 179 (M+ - t-Bu., 1.0, 2.7), 125 (10.4), 123 (28.3), 95 (9.0), 93 (20.3), 75 (10.6), 73 (10.3) 70 (7.6), 69 (100.0); high resolution mass spectrum (70 eV) m/e 181.0636, 179.0656 (calculated 181.0630, 179.0660 for C7H16OClSi). then partitioned between water (200 mL) and OEt2 l (300 mL) The aqueous layer was extracted with more OEt2 (2×100 mL) the combined extract was dried (Na2SO4) The OEt2 was removed the residue fractionally distilled A small fore-run was collected (bp 57° C. (16 mm))

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

Procedure: A mixture of t-butyldimethylsilyl chloride (29.5 g, 0.196 mole) and 5-chloro-1-pentanol (20 g, 0.163 mole) under an inert atmosphere was treated with a solution of imidazole (27.7 g, 0.407 mole) in dry DMF (40 mL). The reaction was stirred overnight at room temperature then partitioned between water (200 mL) and OEt2 l (300 mL). The aqueous layer was extracted with more OEt2 (2×100 mL), and the combined extract was dried (Na2SO4). The OEt2 was removed and the residue fractionally distilled. A small fore-run was collected (bp 57° C. (16 mm)) and then [(5-chloro-1-pentyl)oxy](1,1-dimethylethyl)dimethylsilane as a colorless oil (44.8 g, 97%): bp 120°-5° C. (17 mm), IR (film) cm-1 2960, 2940, 2900, 2865, 1475, 1465, 1390, 1365, 1290, 1260, 1110, 1055, 1030, 1010, 982, 940, 910, 840, 815, 780, 725, 660; 1H NMR (200 MHz, CDCl3) δ 3.62 (t, 6.1 Hz, 2H), 3.54 (t, 6.7 Hz, 2H), 1.79 (pentet, 7 Hz, 2H), 1.52 (m, 4H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (22.5 MHz, CDCl3) δ 62.8, 44.9, 32.5, 32.1, 26.0 (3C), 23.3, 18.3 (tertiary), -5.3 (2C); mass spectrum (70 eV) m/e (% base) 238, 236 (M+, not observed), 181, 179 (M+ - t-Bu., 1.0, 2.7), 125 (10.4), 123 (28.3), 95 (9.0), 93 (20.3), 75 (10.6), 73 (10.3) 70 (7.6), 69 (100.0); high resolution mass spectrum (70 eV) m/e 181.0636, 179.0656 (calculated 181.0630, 179.0660 for C7H16OClSi). then partitioned between water (200 mL) and OEt2 l (300 mL) The aqueous layer was extracted with more OEt2 (2×100 mL) the combined extract was dried (Na2SO4) The OEt2 was removed the residue fractionally distilled A small fore-run was collected (bp 57° C. (16 mm))

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

Procedure: The title compound was prepared from 5-fluoro-3-iodo-indazole and (5-chloropentoxy)tert-butyldimethylsilane in 79% yield according to the general procedure for Preparation 31A. The minor isomer was not isolated or characterized. 1H NMR (400 MHz, CDCl3): δ 0.06 (6H, s), 0.90 (9H, s), 1.34-1.37 (2H, m), 1.50-1.55 (2H, m), 1.90-1.94 (2H, m), 3.55 (2H, t, J=6.4 Hz), 4.37 (2H, t, J=7.2 Hz), 7.10 (1H, dd, J=2.0, 8.0 Hz), 7.19 (1H, td, J=2.4, 8.8 Hz), 7.432 (1H, dd, J=4.0, 9.2 Hz). The minor isomer was not isolated

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

Procedure: A mixture of t-butyldimethylsilyl chloride (29.5 g, 0.196 mole) and 5-chloro-1-pentanol (20 g, 0.163 mole) under an inert atmosphere was treated with a solution of imidazole (27.7 g, 0.407 mole) in dry DMF (40 mL). The reaction was stirred overnight at room temperature then partitioned between water (200 mL) and OEt2 l (300 mL). The aqueous layer was extracted with more OEt2 (2×100 mL), and the combined extract was dried (Na2SO4). The OEt2 was removed and the residue fractionally distilled. A small fore-run was collected (bp 57° C. (16 mm)) and then [(5-chloro-1-pentyl)oxy](1,1-dimethylethyl)dimethylsilane as a colorless oil (44.8 g, 97%): bp 120°-5° C. (17 mm), IR (film) cm-1 2960, 2940, 2900, 2865, 1475, 1465, 1390, 1365, 1290, 1260, 1110, 1055, 1030, 1010, 982, 940, 910, 840, 815, 780, 725, 660; 1H NMR (200 MHz, CDCl3) δ 3.62 (t, 6.1 Hz, 2H), 3.54 (t, 6.7 Hz, 2H), 1.79 (pentet, 7 Hz, 2H), 1.52 (m, 4H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (22.5 MHz, CDCl3) δ 62.8, 44.9, 32.5, 32.1, 26.0 (3C), 23.3, 18.3 (tertiary), -5.3 (2C); mass spectrum (70 eV) m/e (% base) 238, 236 (M+, not observed), 181, 179 (M+ - t-Bu., 1.0, 2.7), 125 (10.4), 123 (28.3), 95 (9.0), 93 (20.3), 75 (10.6), 73 (10.3) 70 (7.6), 69 (100.0); high resolution mass spectrum (70 eV) m/e 181.0636, 179.0656 (calculated 181.0630, 179.0660 for C7H16OClSi). then partitioned between water (200 mL) and OEt2 l (300 mL) The aqueous layer was extracted with more OEt2 (2×100 mL) the combined extract was dried (Na2SO4) The OEt2 was removed the residue fractionally distilled A small fore-run was collected (bp 57° C. (16 mm))

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

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

Procedure: All reactions are carried out under an inert atmosphere. The starting material, (5-chloro-1-pentyloxy)(2,2-dimethylethyl) dimethylsilane {[(5-chloropentyl)oxy](1,1-dimethylethyl)dimethylsilane} (534 g, 2.26 moles), diluted in tetrahydrofuran (500 ml), is added portionwise to a refluxing solution of tetrahydrofuran and granular magnesium (75 g). After the addition is complete the reaction is refluxed an additional 2 hours and the resultant Grignard salt is cooled to room temperature, cannulated into a three liter flask, and cooled to -20° C. A solution of Li2CuCl4 (6.4 mmoles) is added, followed by the dropwise addition of 3-chlorocyclopentene (219 g, 2.1 moles) cooled in a -20° C. dry ice/ethanol bath. After the addition is complete the mixture is warmed to room temperature. Water (500 ml) is added. The reaction mixture is extracted with hexane (3×400 ml). The organic layers are combined, washed with brine (2×500 ml) and dried over anhydrous sodium sulfate. The remaining solvent is removed under vacuum leaving a clear yellow oil. The crude product is fractionally distilled under reduced pressure leaving a clear, colorless oil (478 g, 1.78 moles), BP 96° C./0.3 mm. After the addition is refluxed an additional 2 hours cannulated into a three liter flask cooled to -20° C cooled in a -20° C. dry ice/ethanol bath After the addition is warmed to room temperature The reaction mixture is extracted with hexane (3×400 ml) washed with brine (2×500 ml) dried over anhydrous sodium sulfate The remaining solvent is removed under vacuum leaving a clear yellow oil The crude product is fractionally distilled under reduced pressure

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

Procedure: The title compound was prepared from 5-fluoro-3-iodo-indazole and (5-chloropentoxy)tert-butyldimethylsilane in 79% yield according to the general procedure for Preparation 31A. The minor isomer was not isolated or characterized. 1H NMR (400 MHz, CDCl3): δ 0.06 (6H, s), 0.90 (9H, s), 1.34-1.37 (2H, m), 1.50-1.55 (2H, m), 1.90-1.94 (2H, m), 3.55 (2H, t, J=6.4 Hz), 4.37 (2H, t, J=7.2 Hz), 7.10 (1H, dd, J=2.0, 8.0 Hz), 7.19 (1H, td, J=2.4, 8.8 Hz), 7.432 (1H, dd, J=4.0, 9.2 Hz). The minor isomer was not isolated

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

Procedure: A mixture of t-butyldimethylsilyl chloride (29.5 g, 0.196 mole) and 5-chloro-1-pentanol (20 g, 0.163 mole) under an inert atmosphere was treated with a solution of imidazole (27.7 g, 0.407 mole) in dry DMF (40 mL). The reaction was stirred overnight at room temperature then partitioned between water (200 mL) and OEt2 l (300 mL). The aqueous layer was extracted with more OEt2 (2×100 mL), and the combined extract was dried (Na2SO4). The OEt2 was removed and the residue fractionally distilled. A small fore-run was collected (bp 57° C. (16 mm)) and then [(5-chloro-1-pentyl)oxy](1,1-dimethylethyl)dimethylsilane as a colorless oil (44.8 g, 97%): bp 120°-5° C. (17 mm), IR (film) cm-1 2960, 2940, 2900, 2865, 1475, 1465, 1390, 1365, 1290, 1260, 1110, 1055, 1030, 1010, 982, 940, 910, 840, 815, 780, 725, 660; 1H NMR (200 MHz, CDCl3) δ 3.62 (t, 6.1 Hz, 2H), 3.54 (t, 6.7 Hz, 2H), 1.79 (pentet, 7 Hz, 2H), 1.52 (m, 4H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (22.5 MHz, CDCl3) δ 62.8, 44.9, 32.5, 32.1, 26.0 (3C), 23.3, 18.3 (tertiary), -5.3 (2C); mass spectrum (70 eV) m/e (% base) 238, 236 (M+, not observed), 181, 179 (M+ - t-Bu., 1.0, 2.7), 125 (10.4), 123 (28.3), 95 (9.0), 93 (20.3), 75 (10.6), 73 (10.3) 70 (7.6), 69 (100.0); high resolution mass spectrum (70 eV) m/e 181.0636, 179.0656 (calculated 181.0630, 179.0660 for C7H16OClSi). then partitioned between water (200 mL) and OEt2 l (300 mL) The aqueous layer was extracted with more OEt2 (2×100 mL) the combined extract was dried (Na2SO4) The OEt2 was removed the residue fractionally distilled A small fore-run was collected (bp 57° C. (16 mm))