Lithium borohydride → HCID 86627070, compound

Temperature

0 °C

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).

1. temperaturemaintaining an internal temperature lower than 10° C
2. customhad been consumed
3. additionAt 0° C., a mixture of saturated ammonium chloride in water (2.5 L) and water (2.5 L)
4. additionwas added slowly
5. temperaturemaintaining an internal temperature lower than 10° C
6. temperatureto warm to ambient temperature, at which point the THF layer
7. customwas separated
8. concentrationThe THF layer was concentrated to about 2 L
9. extractionthe aqueous layer was extracted twice with ethyl acetate (4 L)
10. washwashed twice with water (4 L)
11. washThe organic layer was then washed with saturated sodium chloride in water (4 L)
12. concentrationconcentrated

ORD record

ord-387d89fa79df49259d27602c5ef45134

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933225B2