1-Bromo-4-(trifluoromethoxy)benzene → 1-Boc-4-[Hydroxy-(4-trifluoromethoxyphenyl)methyl]piperidine

HRID 1726127Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[Li]CCCC.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([CH:31]=[O:32])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>C1COCC1>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([CH:31]([OH:32])[C:2]2[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-bromo-4-(trifluoromethoxy)benzene (1.88 g, 7.80 mmol) in THF (16 mL) at −78° C. was added n-BuLi (1.9M in hexanes, 4.1 mL, 7.8 mmol), and the solution was stirred at −78° C. for 30 minutes. A solution of 4-formyl-piperidine-1-carboxylic acid tert-butyl ester (1.50 g, 7.03 mmol) in THF (2 mL) was added dropwise, and the mixture was stirred at −78° C. for 45 minutes then allowed to warm to room temperature over 1 h. Work-up and purification gave 4-[hydroxy-(4-trifluoromethoxy-phenyl)-methyl]-piperidine-1-carboxylic acid tert-butyl ester as colourless crystals (1.75 g, 66%).

Workup

stirringthe mixture was stirred at −78° C. for 45 minutes
temperatureto warm to room temperature over 1 h
custompurification

Sources & evidence

ORD record: ord-e7a88e6e918f4f039f054724f682ebce
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07491735B2

Reaction notes

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