Methyl iodide → 1-Tert-butoxycarbonyl-4-(4-chlorophenyl)-4-methoxypiperidine

HRID 1977286Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].IC.[C:26](OCC)(=O)C>CN(C)C=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)([O:14][CH3:26])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 1-tert-butoxycarbonyl-4-(4-chlorophenyl)-4-hydroxypiperidine (1.0 g) in N,N-dimethyl formamide (10 ml) was added sodium hydride (0.14 g) under ice cooling. Then the reaction mixture was stirred for 30 minutes at room temperature and for 2 hours at 60° C. To the reaction mixture was added iodomethane (4.0 ml) at 60° C. After stirring for 6 hours at 60° C., the reaction mixture was poured into a mixture of ethyl acetate and water. The organic layer was successively washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was purified by column chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (10:1). The eluted fractions containing the desired product were collected and evaporated in vacuo to give 1-tert-butoxycarbonyl-4-(4-chlorophenyl)-4-methoxypiperidine (0.75 g).

Workup

stirringAfter stirring for 6 hours at 60° C.
washThe organic layer was successively washed with brine
dry with materialdried over magnesium sulfate
customThe solvent was evaporated in vacuo
customthe residue was purified by column chromatography on silica gel eluting with a mixture of hexane and ethyl acetate (10:1)
additionThe eluted fractions containing the desired product
customwere collected
customevaporated in vacuo

Sources & evidence

ORD record: ord-f680188077d64b7bbbbd1c93abeea9b4
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06232290B1

Reaction notes

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