| 84% |
With pyridine In dichloromethane at 0℃; for 1.5 h; |
A solution of pyridine (1.7 mL) in 10 mL of CH2Cl2 was added dropwise over 10 min to a 0 °C solution of (1-methyl)cyclopropanol (1300 mg, 17 mmol) and 4-nitrophenyl chloroformate (3842 mg, 19 mmol) in 50 mL of CH2Cl2. The mixture was stirred for 90 min, then quenched with 50 mL of 0.1 M*H2SO4. The CH2Cl2 phase was washed with water, NaHCO3, brine, and dried (MgSO4). The MgSO4 was filtered and the filtrate was diluted with twice its volume of hexane. A solid precipitate formed gradually. The mixture was filtered and the filtrate was concentrated to dryness to afford a colorless semisolid. This residue was digested with 50 mL of hexane, filtered while hot and the solid was washed with 2 .x. 10 mL of boiling hexane. The filtrate was concentrated to afford 2 as a white solid, mp 46-48 °C. 1H NMR (CDCl3) δ 0.72-0.82 (m, 2H), 1.02-1.15 (m, 2H), 1.66 (s, 3H), 7.38 (m, 2H), 8.27 (m, 2H). Calcd for C11H11NO5: C 55.70percent; H 4.67percent; N 5.90percent. Found: C 55.52percent, H 4.52percent, N 5.94percent. It is important that Et3N not be used in this reaction as it reacts with the chloroformate |
| 20.8 g |
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 14 h; |
B) 1 -Methylcvclopropyl 4-nitrophenyl carbonateA solution of 1 -methylcyclopropanol (10 g, 137 mmol), 4-nitrophehyl chloroformate (32 g, 152 mmol), and a few crystals of 4-dimethylaminopyridine (150 mg, 1 .2 mmol) in dichloromethane (462 mL), was cooled to zero degree Celsius. Triethylamine (36.5 g, 361 mmol) was added drop-wise. After 10 minutes, the ice bath was removed and the reaction was allowed to stir at room temperature for 14 hours. The reaction mixture was washed twice with saturated aqueous sodium carbonate. The aqueous phase was extracted with dichloromethane. The combined organic extracts were washed with water, dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo. The residue was purified by flash silica gel chromatography, eluting with a gradient mixture of ethyl acetate in heptane (0 to 5percent ethyl acetate over the first 10 minutes, then isocratic at 5percent ethyl acetate to heptane) to give 20.8 g of the desired carbonate as a clear oil. This oil solidified upon standing.1 H NMR (500 MHz, deuterochloroform) delta 0.77 (app. t, =6.59 Hz, 2 H), 1 .09 (app. t, J=7.07 Hz, 2 H), 1.67 (s, 3 H), 7.40 (app. dt, J=9.27, 3.17 Hz, 2 H), 8.29 (app. dt, J=9.27, 3.17 Hz, 2 H). |
| 3.21 g |
With pyridine In dichloromethane at 5℃; for 1.66667 h; |
4-Nitrophenyl chloroformate (3; 3.84 g, 19 mmol) was dissolved in CH2Cl2 (40 mL) and cooled to <5 °C. To this was added a cold solution of 1 (1.30 g, 17 mmol) in CH2Cl2 (10 mL), previously dried with Na2SO4. A solution of pyridine (1.7 mL, 21 mmol) in CH2Cl2 (10 mL) was added dropwise with stirring over 10 min with continued cooling. The mixture was stirred for an additional 90 min, then quenched with 0.1 M H2SO4 (50 mL). The CH2Cl2 layer was washed with H2O (25 mL), aq NaHCO3 (25 mL), brine (25 mL), and dried (MgSO4). After filtration, the CH2Cl2 layer was diluted with twice its volume of hexane. A white precipitate of bis(4-nitrophenyl)carbonate formed gradually. This was filtered and discarded. The filtrate was concentrated to dryness to afford 3.99 g of a colorless semisolid. This was digested with hexane (50 mL) under reflux, filtered while hot, and the precipitate was washed with boiling hexane (2 × 10 mL). The filtrate was concentrated to give 3.42 g of a white solid, which was recrystallized from hexane (5 mL) to afford 3.21 g (79percent) of analytically pure 2; mp 46–48 °C. IR (film): 1770, 1524, 1349 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.72–0.82 (m, 2 H), 1.02–1.15 (m,2 H), 1.66 (s, 3 H), 7.38 (d, J = 9.4 Hz, 2 H), 8.27 (d, J = 9.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ = 12.85, 20.48, 60.64, 121.67, 125.19, 145.24, 151.89, 155.41. Anal. Calcd for C11H11NO5: C, 55.70; H, 4.67; N, 5.90. Found: C,55.52; H, 4.52; N, 5.94. |
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