Sodium hydride → (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2,2-dimethoxypropoxy)methyl)piperidine-1-carboxylate

HRID 451916Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:22])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:26][C:27]([O:31][CH3:32])([O:29][CH3:30])[CH3:28]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:22][CH2:26][C:27]([O:31][CH3:32])([O:29][CH3:30])[CH3:28])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (0.2234 g, 0.68 mmol), 60% NaH (1.460 g, 36.5 mmol), and 1-bromo-2,2-dimethoxypropane (7.760 g, 42.4 mmol) in THF (20 mL) was heated at 80° C. for 3 d and then cooled to rt. The reaction mixture was then quenched with water, extracted with ethyl acetate (3×), and dried over Na2SO4. After the solvent was evaporated under reduced pressure, the crude product (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2,2-dimethoxypropoxy)methyl)piperidine-1-carboxylate was directly used in the next step without further purification.

Workup

temperaturecooled to rt
customThe reaction mixture was then quenched with water
extractionextracted with ethyl acetate (3×)
dry with materialdried over Na2SO4
customAfter the solvent was evaporated under reduced pressure
customthe crude product (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2,2-dimethoxypropoxy)methyl)piperidine-1-carboxylate was directly used in the next step without further purification

Sources & evidence

ORD record: ord-b745b5923a5b42bcaae61184481f9155
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08487108B2

Reaction notes

Loading…