Water → HCID 86696732, compound

Temperature

-78 °C

(R)-tert-Butyl 3-(4-chloro-3-fluorobenzoyl)pyrrolidine-1-carboxylate (920 mg, 2.806 mmol) was dissolved in THF (14.0 mL, 0.2M), degassed with N2, and cooled to −78° C. Lithium tri-sec-butylborohydride (1M in THF; 4210 μL, 4.210 mmol) was added slowly drop wise by syringe. The reaction was then stirred at −78° C. for 30 minutes. Water (5 mL) was then added to quench the reaction. The mixture was concentrated by rotovap to remove the bulk of the THF. The remaining mixture was diluted to 50 mL with water and extracted with 4/1 dichloromethane/isopropyl alcohol (2×50 mL). The combined organics were washed with water (100 mL), were isolated, dried over sodium sulfate, filtered and concentrated. The crude product was loaded onto an SP1 samplet and purified by silica gel chromatography using a gradient from 1% to 55% ethyl acetate in hexanes. Product containing fractions were pooled and concentrated to afford (3R)-tert-butyl 3-((4-chloro-3-fluorophenyl)(hydroxy)methyl)pyrrolidine-1-carboxylate as an oil and as a 1:1 mixture of diastereomers (640 mg, 69% yield).

1. customdegassed with N2
2. customto quench
3. customthe reaction
4. concentrationThe mixture was concentrated by rotovap
5. customto remove the bulk of the THF
6. additionThe remaining mixture was diluted to 50 mL with water
7. extractionextracted with 4/1 dichloromethane/isopropyl alcohol (2×50 mL)
8. washThe combined organics were washed with water (100 mL)
9. customwere isolated
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. custompurified by silica gel chromatography
14. additionProduct containing fractions
15. concentrationconcentrated

ORD record

ord-9762b7d7f37740c6a8a441917c133085

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09259470B2