(3S,4R)-1-(tert-Butoxycarbonyl)-4-(4-fluorophenyl)piperidine-3-carboxylic acid → tert-Butyl (3S,4R)-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine-1-carboxylate

HRID 2039798Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (−)-(3S,4R)-4-(4-fluoro-phenyl)-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (1.71 g, 5.29 mmol) in 35 ml THF was added a 2 M borane dimethylsulfide complex solution in THF (5.44 ml, 10.9 mmol) at 0° C. The mixture was stirred for 15 min at 0° C. and then at room temperature over night. After cooling to 0° C. the reaction was quenched by the addition of methanol. Stirring was continued until no evolution of gas was observed any more. The reaction mixture was diluted with water and extracted with 3 portions of tert-butyl methyl ethyl. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Flash chromatography gave 1.58 g (94%) of the title compound as a colorless viscous oil.

Workup

waitat room temperature over night
temperatureAfter cooling to 0° C. the reaction
customwas quenched by the addition of methanol
stirringStirring
additionThe reaction mixture was diluted with water
extractionextracted with 3 portions of tert-butyl methyl ethyl
dry with materialThe combined organic layers were dried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-e77f0d977fba4a7d8959cbb8b0b0d074
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580821B2

Reaction notes

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