(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 253080Notes

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-165a5b53cb624f9f9c9cea4f607c1a9b
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07872022B2

Reaction notes

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