Toluene → (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate

HRID 218384Notes

Reaction equation

B.C1(C)C=CC=CC=1.[Cl:9][C:10]1[CH:11]=[C:12]([CH:28]=[C:29]([F:31])[CH:30]=1)[C:13]([C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1)=[O:14]>C1COCC1>[Cl:9][C:10]1[CH:11]=[C:12]([C@H:13]([OH:14])[C@@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:16]2)[CH:28]=[C:29]([F:31])[CH:30]=1

Participants

Conditions

Temperature: -15 °C

Procedure

A mixture of 10 M H3B.S2Me in THF (47.7 mL, 0.477 mol) and 1 M R-CBS-oxazaborolidine in toluene (72 mL, 0.072 mol) were dissolved in 100 mL anhydrous THF and cooled to −15° C. (R)-tert-butyl 3-(3-chloro-5-fluorobenzoyl)piperidine-1-carboxylate in 400 mL anhydrous THF was added dropwise to the above solution and stirred at −15° C. for 2 hr. The reaction was quenched with methanol (500 mL). The solvent was removed under reduced pressure and the residue was purified by column chromatography. The product was re-crystallized three times with EtOAc/Hexanes to give (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (55 g, 0.156 mol). 1H NMR (CDCl3, 400 MHz) δ 7.10 (s, 1H), 7.04-6.90 (dd, 2H), 4.46-4.30 (d, 1H), 4.05-2.40 (m, 5H), 1.74 (s, 1H), 1.60 (s, 1H), 1.53-1.31 (m, 1H), 1.30-1.14 (m, 1H).

Workup

additionwas added dropwise to the above solution
customThe reaction was quenched with methanol (500 mL)
customThe solvent was removed under reduced pressure
customthe residue was purified by column chromatography
customThe product was re-crystallized three times with EtOAc/Hexanes

Sources & evidence

ORD record: ord-b97852c82b9a4c25a7f7c2fba0fa3f96
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198453B2

Reaction notes

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