tert-butyl N-(1-hydroxy-3-methylbutan-2-yl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared using the method of Example 34(c) starting from 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile (0.2 g; 0.98 mmol) and tert-butyl 1-hydroxy-3-methylbutan-2-ylcarbamate (0.22 g; m 1.09 mmol). Yield 22%. 1H-NMR (400 MHz; CDCl3): δ 1.02 (m, 6H), 1.71 (m, 1H), 3.14 (m, 1H), 3.95 (m, 1H), 4.27 (m, 1H), 6.61 (d, 1H), 7.51 (d, 1H), 7.66 (d, 1H), 7.77 (dd, 1H), 7.97 (s, 1H).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared using the method of Example 34(c) starting from 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile (0.2 g; 0.98 mmol) and tert-butyl 1-hydroxy-3-methylbutan-2-ylcarbamate (0.22 g; m 1.09 mmol). Yield 22%. 1H-NMR (400 MHz; CDCl3): δ 1.02 (m, 6H), 1.71 (m, 1H), 3.14 (m, 1H), 3.95 (m, 1H), 4.27 (m, 1H), 6.61 (d, 1H), 7.51 (d, 1H), 7.66 (d, 1H), 7.77 (dd, 1H), 7.97 (s, 1H).

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1.75 g of tert-butyl 1-hydroxy-3-methylbutan-2-ylcarbamate (Formula 20) in 25 mL of DMSO was added 3.6 mL of triethylamine. The solution was cooled to 0° C. and 4.1 grams of sulfur trioxide pyridine complex in 25 mL of DMSO was added. The reaction mixture was stirred at room temperature for 1 hour. Then, the mixture was poured onto ice-water and extracted with ethyl acetate. The organic layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine, dried over sodium sulfate and concentrated. Column chromatography (30% ethyl acetate/hexane) gave 1.25 g of tert-butyl 3-methyl-1-oxobutan-2-ylcarbamate (Formula 21) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 0.95 (d, J=7.32 Hz, 3H), 1.03 (d, J=6.83 Hz, 3H), 1.45 (s, 9H), 2.27-2.29 (m, 1H), 4.24-4.26 (m, 1H), 9.65 (s, 1H). Then, the mixture was poured onto ice-water extracted with ethyl acetate The organic layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine dried over sodium sulfate concentrated

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Methylbenzenesulfonyl chloride (0.2222 mol) was added portionwise at 10° C. to a mixture of 1,1-dimethylethyl [1-(hydroxymethyl)-2-methylpropyl]carbamoate (0.202 mol) in pyridine (65 ml). The mixture was stirred at 10° C. for 2 hours. H2O (75 ml) was added at 10° C. The precipitate was filtered off, washed with H2O and taken up in CH2Cl2. The organic solution was washed with H2O, dried, filtered and the solvent was evaporated, yielding 49 g of (±)-1,1-dimethylethyl [1-[[[(4-methylphenyl)-sulfonyl]oxy]methyl]-2-methylpropyl]carbamate (68%) (interm. 13). The precipitate was filtered off washed with H2O The organic solution was washed with H2O dried filtered the solvent was evaporated

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Methylbenzenesulfonyl chloride (0.2222 mol) was added portionwise at 10° C. to a mixture of 1,1-dimethylethyl [1-(hydroxymethyl)-2-methylpropyl]carbamoate (0.202 mol) in pyridine (65 ml). The mixture was stirred at 10° C. for 2 hours. H2O (75 ml) was added at 10° C. The precipitate was filtered off, washed with H2O and taken up in CH2Cl2. The organic solution was washed with H2O, dried, filtered and the solvent was evaporated, yielding 49 g of (±)-1,1-dimethylethyl [1-[[[(4-methylphenyl)-sulfonyl]oxy]methyl]-2-methylpropyl]carbamate (68%) (interm. 13). The precipitate was filtered off washed with H2O The organic solution was washed with H2O dried filtered the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared using the method of Example 34(c) starting from 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile (0.2 g; 0.98 mmol) and tert-butyl 1-hydroxy-3-methylbutan-2-ylcarbamate (0.22 g; m 1.09 mmol). Yield 22%. 1H-NMR (400 MHz; CDCl3): δ 1.02 (m, 6H), 1.71 (m, 1H), 3.14 (m, 1H), 3.95 (m, 1H), 4.27 (m, 1H), 6.61 (d, 1H), 7.51 (d, 1H), 7.66 (d, 1H), 7.77 (dd, 1H), 7.97 (s, 1H).

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1.75 g of tert-butyl 1-hydroxy-3-methylbutan-2-ylcarbamate (Formula 20) in 25 mL of DMSO was added 3.6 mL of triethylamine. The solution was cooled to 0° C. and 4.1 grams of sulfur trioxide pyridine complex in 25 mL of DMSO was added. The reaction mixture was stirred at room temperature for 1 hour. Then, the mixture was poured onto ice-water and extracted with ethyl acetate. The organic layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine, dried over sodium sulfate and concentrated. Column chromatography (30% ethyl acetate/hexane) gave 1.25 g of tert-butyl 3-methyl-1-oxobutan-2-ylcarbamate (Formula 21) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 0.95 (d, J=7.32 Hz, 3H), 1.03 (d, J=6.83 Hz, 3H), 1.45 (s, 9H), 2.27-2.29 (m, 1H), 4.24-4.26 (m, 1H), 9.65 (s, 1H). Then, the mixture was poured onto ice-water extracted with ethyl acetate The organic layers were washed with 10% acetic acid, water, 5% sodium bicarbonate, and brine dried over sodium sulfate concentrated