Hydrogen Peroxide → (S)-3-(tert-butoxycarbonyl(cyclopropylmethyl)amino)-2-(4-chlorophenyl)propanoic acid

LiOH (1.41 g, 33.5 mmol) was added to a flask containing THF (360 mL) and H2O (120 mL), which was stirred until dissolved. At this point, the reaction was cooled to 0° C. with ice, and hydrogen peroxide (35 wt. %, 6.52 g) was added. This solution was stirred for 10 minutes, at which point tert-butyl (S)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-2-(4-chlorophenyl)-3-oxopropyl(cyclopropylmethyl)carbamate (8.6 g, 16.8 mmol) was added as a solution in THF (20 mL). The reaction was stirred overnight with warming. The reaction was quenched by the addition of 10% aqueous Na2SO3 (1 mL) and saturated aqueous NaHCO3 (1 mL) and stirred for 10 minutes. The reaction was concentrated to remove THF and the aqueous layer extracted with ether (3×). The aqueous layer was diluted with EtOAc and acidified with 1N HCl. The organic layer was removed, and the aqueous layer was extracted with EtOAc (2×). The combined organics were dried with MgSO4 and concentrated to give the crude product, (S)-3-(tert-butoxycarbonyl(cyclopropylmethyl)amino)-2-(4-chlorophenyl)propanoic acid as a clear oil (LCMS (APCI+) [M−Boc+H]+ 254.1; Rt: 3.03 min).

1. dissolutionuntil dissolved
2. additionwas added
3. stirringThe reaction was stirred overnight
4. temperaturewith warming
5. customThe reaction was quenched by the addition of 10% aqueous Na2SO3 (1 mL) and saturated aqueous NaHCO3 (1 mL)
6. stirringstirred for 10 minutes
7. concentrationThe reaction was concentrated
8. customto remove THF
9. extractionthe aqueous layer extracted with ether (3×)
10. additionThe aqueous layer was diluted with EtOAc
11. customThe organic layer was removed
12. extractionthe aqueous layer was extracted with EtOAc (2×)
13. dry with materialThe combined organics were dried with MgSO4
14. concentrationconcentrated

ORD record

ord-df94dd66ce924e4cae00e0b44e946002

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853199B2