Ammonia → (1S,2S,4R)-4-carbamoyl-2-methoxycyclopentyl nitrate

Temperature

0 °C

To a dichloromethane solution (30 mL) of (1R,3S,4S)-3-methoxy-4-(nitrooxy)cyclopentanecarboxylic acid (example 1, 0.13 g, 0.64 mmol) was added triethylamine (0.72 mL, 5.1 mmol) and ethyl chlorofonnate (0.49 mL, 5.1 mmol) at 0° C. The reaction solution was stirred at 0° C. for 1 hour when aqueous ammonia (8.0 mL, 0.10 mol, 28% wt) was added. The reaction was stirred for another 16 hours at 0° C. The aqueous phase was extracted with dichloromethane (2×15 mL). The combined organics were washed with cold 5% sodium bicarbonate (30 mL) and dried over magnesium sulfate. The organics were concentrated in vacuo and purified by column chromatography, affording the title compound as a colorless liquid. 1H NMR (500 MHz, CDCl3) δ 2.02 (ddd, J=3.7, 6.1, 14.5 Hz, 1H), 2.22 (dd, J=8.5, 15.3 Hz, 1H), 2.30-2.37 (m, 1H), 2.40-2.47 (m, 1H), 2.94 (quintet, J=6.2 Hz, 1H), 3.44 (s, 3H), 3.89-3.91 (m, 1H), 5.36 (d, J=6.1 Hz, 1H).

1. additionwas added
2. extractionThe aqueous phase was extracted with dichloromethane (2×15 mL)
3. washThe combined organics were washed with cold 5% sodium bicarbonate (30 mL)
4. dry with materialdried over magnesium sulfate
5. concentrationThe organics were concentrated in vacuo
6. custompurified by column chromatography

ORD record

ord-ed104f620b9745569985cbbfd9d5ff61

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08530521B2