Lithium aluminum hydride → HCID 86717516, compound

Temperature

0 °C

Methyl (1S,2S,4S)-4-[(tert-butoxycarbonyl)amino]-2-methoxycyclohexanecarboxylate (racemic) (1.02 g, 3.55 mmol) were dissolved in ether (32 mL) and cooled to 0° C. Lithium tetrahydroaluminate (162 mg, 4.26 mmol) was added and the resulting mixture was stirred for 4 h. The reaction was quenched with 5 mL water at 0° C., then diluted with 5 mL 15% NaOH and 15 mL water after stirring for 30 min. The reaction mixture was filtered through a pad of Celite and washed with ethyl acetate. The aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude was purified with flash chromatography (eluting with a gradient of 0-80% ethyl acetate in hexanes) to give the desired product as white foam. LCMS calculated for C8H18NO2 (M+H-Boc)+: m/z=160.1. Found: 160.2. 1H NMR (300 MHz, CDCl3) δ 4.46 (1H, brs), 3.71-3.40 (3H, m), 3.37 (3H, s), 3.12 (2H, m), 2.48 (1H, m), 1.94 (1H, m), 1.71-1.50 (3H, m), 1.41 (9H, s), 1.05 (2H, m) ppm.

1. customThe reaction was quenched with 5 mL water at 0° C.
2. additiondiluted with 5 mL 15% NaOH and 15 mL water
3. stirringafter stirring for 30 min
4. filtrationThe reaction mixture was filtered through a pad of Celite
5. washwashed with ethyl acetate
6. extractionThe aqueous layer was extracted with ethyl acetate (2×)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude was purified with flash chromatography (
12. washeluting with a gradient of 0-80% ethyl acetate in hexanes)

ORD record

ord-b1e4087558f243e2bd9d7c6106644069

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181271B2