(S)-tert-butyl 3-formylpyrrolidine-1-carboxylate → (35)-Tert-butyl 3-((3-chloro-4-fluorophenyl)(hydroxy)methyl)pyrrolidine-1-carboxylate

To a stirred solution of (S)-tert-butyl 3-formylpyrrolidine-1-carboxylate (67)(367.3 mg, 1.843 mmol) in THF (9.2 mL, 0.2 M) under nitrogen atmosphere cooled to 0° C. and degassed with N2 was added dropwise a THF solution of (3-chloro-4-fluorophenyl)magnesium bromide (4056 μL, 2.028 mmol) and the solution stirred at 0° C. for 3 h. The reaction was then quenched by addition of water (3 mL) THF was removed by rotovap, and the mixture was extracted with EtOAc (2×30 mL). The combined organics were washed with water (2×30 mL) and brine (1×30 mL). The organic extracts were dried (Na2SO4), filtered and concentrated. The crude product was loaded onto an SP1 samplet and purified by chromatography eluting a DCM/acetone gradient (2 to 45% acetone) to afford 364 mg (60%) of 69a/69b as an approximate 1:1 mixture of diastereomers as a clear oil which was used without additional purification.

1. customdegassed with N2
2. customThe reaction was then quenched by addition of water (3 mL) THF
3. customwas removed by rotovap
4. extractionthe mixture was extracted with EtOAc (2×30 mL)
5. washThe combined organics were washed with water (2×30 mL) and brine (1×30 mL)
6. dry with materialThe organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. custompurified by chromatography
10. washeluting a DCM/acetone gradient (2 to 45% acetone)

ORD record

ord-6705784cb7ea45008a74ba87b4eccf1f

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187462B2