Lithium tri-s-butylborohydride → (R)-tert-butyl 2-((R)-(4-chloro-3-fluorophenyl)(hydroxy)methyl)pyrrolidine-1-carboxylate

HRID 2365824Notes

Reaction equation

[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([C:6]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:7])=[CH:4][C:3]=1[F:22].CCC(C)[BH-](C(C)CC)C(C)CC.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([C@@H:6]([OH:7])[C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])=[CH:4][C:3]=1[F:22]

Participants

Conditions

Temperature: -78 °C

Procedure

(R)-tert-Butyl 2-(4-chloro-3-fluorobenzoyl)pyrrolidine-1-carboxylate (1.12 g, 3.42 mmol) was placed in THF (50 mL) at −78° C., and 1.0M L-Selectride® (5.13 mL, 5.13 mmol) as a solution in THF was added. The reaction was stirred at −78° C. for 1 hour and then 0° C. for 2 hours. The reaction was quenched with 1N HCl, and the pH was adjusted to about 7 with saturated NaHCO3. The mixture was concentrated to remove most of the THF, and the residue was extracted with ethyl acetate (2×). The combined organics were dried, filtered and concentrated. The crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (12:1) to give (R)-tert-butyl 2-((R)-(4-chloro-3-fluorophenyl)(hydroxy)methyl)pyrrolidine-1-carboxylate (0.67 g, 60%). m/z (APCI-pos) (M+1)-Boc=230.1, 232.1.

Workup

wait0° C. for 2 hours
customThe reaction was quenched with 1N HCl
concentrationThe mixture was concentrated
customto remove most of the THF
extractionthe residue was extracted with ethyl acetate (2×)
customThe combined organics were dried
filtrationfiltered
concentrationconcentrated
customThe crude product was purified via column chromatography
washeluting with hexanes/ethyl acetate (12:1)

Sources & evidence

ORD record: ord-c68cf76fad1940e9a2363286c5e2be28
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697715B2

Reaction notes

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