1-Bromo-4-phenylmethoxybenzene → (R)-4-(4-benzyloxy-phenyl)-1-(1-phenyl-ethyl)-piperidin-4-ol

HRID 650728Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[C:21]1([C@H:27]([N:29]2[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]2)[CH3:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1.CCCCCC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:32]2([OH:35])[CH2:33][CH2:34][N:29]([C@@H:27]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH3:28])[CH2:30][CH2:31]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -75 °C

Procedure

175.2 g (666 mmol) of 4-benzyloxybromobenzene was dissolved in 1.4 L dry THF (MS 4 A) under argon. The solution was cooled to −75° C. and a solution of 416 mL 1.6 M butyllithium (666 mmol) in hexane was added during 40 min. After stirring for 1 h a solution of 113 g (555 mmol) (R)-1-(1-phenyl-ethyl)-piperidin-4-one in 400 mL dry THF was added during 1 h at −75° C. The mixture was stirred for another 1 h and, after heating to room temperature, poured into 1.5 L of ice water. The mixture was extracted with 1 L ethyl acetate. The organic phase was washed with 1 L of a half-saturated NaCl solution, dried over Na2SO4 and concentrated to yield 262 g of (R)-4-(4-benzyloxy-phenyl)-1-(1-phenyl-ethyl)-piperidin-4-ol.

Workup

additionwas added during 1 h at −75° C
temperatureafter heating to room temperature
extractionThe mixture was extracted with 1 L ethyl acetate
washThe organic phase was washed with 1 L of a half-saturated NaCl solution
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-4deb3435d0494b70a2301470c2e1bc2f
Source dataset: uspto-grants-2001_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06274735B1

Reaction notes

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