Sodium hydride → tert-butyl (3RS,4RS)-4-(4-fluorophenyl)-3-(4-methoxy-benzyloxy)-piperidine-1-carboxylate

HRID 1858558Notes

Reaction equation

HRID 1858558 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=1.[H-].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:10][CH:9]2[O:21][CH2:28][C:27]2[CH:30]=[CH:31][C:24]([O:23][CH3:22])=[CH:25][CH:26]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 45074236Tert-butyl 4-(4-fluorophenyl)-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 86604390tert-butyl (3RS,4RS)-4-(4-fluorophenyl)-3-(4-methoxy-benzyloxy)-piperidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

200 mg (0.68 mmol) of tert-butyl (3RS,4RS)-4-(4-fluorophenyl)-3-hydroxy-piperidine-1-carboxylate and 159 mg (1.01 mmol) of 4-methoxybenzyl chloride were dissolved in 3 ml of dimethylformamide. 40 mg (1.01 mmol) of a 60% sodium hydride suspension were added and the mixture was stirred at room temperature for 3 hours. Subsequently, the reaction mixture was partitioned between ethyl acetate and water, the organic phase was dried over magnesium sulphate and finally the solvent was removed under reduced pressure. The crude product was purified by chromatography on silica gel with a 1:3 mixture of ethyl acetate and hexane as the eluent. There were obtained 250 mg (90% of theory) of tert-butyl (3RS,4RS)-4-(4-fluorophenyl)-3-(4-methoxy-benzyloxy)-piperidine-1-carboxylate as a light yellow oil; MS: 358 (M-C4H9)+.

Workup

  1. customSubsequently, the reaction mixture was partitioned between ethyl acetate and water
  2. dry with materialthe organic phase was dried over magnesium sulphate
  3. customfinally the solvent was removed under reduced pressure
  4. customThe crude product was purified by chromatography on silica gel with a 1:3 mixture of ethyl acetate and hexane as the eluent

Sources & evidence

ORD record
ord-a0e73991a7a746e3873a192c5b0b6fa4
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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