tert-butyl ((1R,2R,3R,4S)-2-bromo-3-hydroxy-4-(hydroxymethyl)cyclopentyl)carbamate synthesis

Yield:1113025-58-3 99%

Reaction Conditions:

Stage #1: tert-butyl [(1R,3R,4R,5R)-4-bromo-7-oxo-6-oxabicyclo-[3.2.0]hept-3-yl]carbamatewith lithium tetrahydridoborate in tetrahydrofuran at 0; for 0.5 h;
Stage #2: with ammonia hydrochloride in tetrahydrofuran;lithium hydroxide monohydrate at 0 - 20;

Steps:

25 Tert-butyl [(1R,2R,3R,4S)-2-bromo-3-hydroxy-4-(hydroxymethyl)cyclopentyl]carbamate

Tert-butyl [(1R,3R,4R,5R)-4-bromo-7-oxo-6-oxabicyclo[3.2.0]hept-3-yl]carbamate (450.0 g, 1.470 mol) was dissolved in THF (6 L) and the mixture was cooled to 0° C. 2.0M lithium tetrahydroborate in THF (730 ml) was added slowly, maintaining an internal temperature lower than 10° C. The mixture was then stirred at 0° C. for 30 minutes, after which HPLC indicated that the starting material had been consumed. At 0° C., a mixture of saturated ammonium chloride in water (2.5 L) and water (2.5 L) was added slowly, maintaining an internal temperature lower than 10° C. The mixture was then allowed to warm to ambient temperature, at which point the THF layer was separated. The THF layer was concentrated to about 2 L, and the aqueous layer was extracted twice with ethyl acetate (4 L). The organic layers were combined and washed twice with water (4 L). The organic layer was then washed with saturated sodium chloride in water (4 L) and concentrated to yield the title compound (452 g, 99%) as a yellow residue. ¹H NMR (300 MHz, CDCl3): δ 4.83 (m, 1H), 4.54 (m, 1H), 4.43 (m, 1H), 4.31 (m, 1H), 3.87 (m, 1H), 3.74 (m, 1H), 2.71 (m, 1H), 2.02 (m, 1H), 1.70 (m, 1H) and 1.41 (bs, 9H).

References:

US2009/36678,2009,A1 Location in patent:Page/Page column 30