Water → 4-(3,5-Dimethylphenyl)-1-(phenylmethyl)-4-piperidinol

HRID 1241879Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[Li]CCCC.[CH2:15]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O>C1COCC1.CCCCCC>[NH4+:22].[OH-:28].[CH2:15]([N:22]1[CH2:27][CH2:26][C:25]([C:2]2[CH:3]=[C:4]([CH3:9])[CH:5]=[C:6]([CH3:8])[CH:7]=2)([OH:28])[CH2:24][CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

Conditions

Temperature: -50 °C

Procedure

5 mL (36.8 mmol) of 5-bromo-m-xylene were dissolved in 40 mL of dry THF under a nitrogen atmosphere. The resulting solution was cooled to −50° C. and 36.5 mL (58.4 mmol) of a 1.6 M solution of n-BuLi in hexane were added dropwise. The reaction mixture was stirred 30 min, then a solution of 10.3 mL (58.4 mmol) of 1-benzyl-4-piperidone in 20 mL of dry THF was added dropwise; stirring was continued for 1 h at −50° C., then the reaction mixture was allowed to warm to room temperature overnight. Water was added carefully and TIF was removed in vacuo; the resulting aqueous solution was extracted with AcOEt, the organic phase was dried and the solvent was removed in vacuo. The resulting crude product was purified by flash chromatography, eluting with a mixture CH2Cl2/MeOH/conc. NH4OH 100:2:0.4 respectively, yielding 5.44 g of the title compound.

Workup

stirringstirring
waitwas continued for 1 h at −50° C.
temperatureto warm to room temperature overnight
customTIF was removed in vacuo
extractionthe resulting aqueous solution was extracted with AcOEt
customthe organic phase was dried
customthe solvent was removed in vacuo
customThe resulting crude product was purified by flash chromatography
washeluting with a mixture CH2Cl2/MeOH/conc

Sources & evidence

ORD record: ord-a7db0c8890224717b9355bad3c68839e
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07115633B2

Reaction notes

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