Sodium hydride → tert-Butyl 4-(4-chlorophenyl)-4-cyanopiperidine-1-carboxylate

HRID 242564Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][C:7]#[N:8])=[CH:4][CH:3]=1.[C:11]([O:15][C:16](=[O:24])[N:17]([CH2:21][CH2:22]Cl)[CH2:18][CH2:19]Cl)([CH3:14])([CH3:13])[CH3:12].[H-].[Na+]>CN(C)C=O>[C:11]([O:15][C:16]([N:17]1[CH2:21][CH2:22][C:6]([C:5]2[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=2)([C:7]#[N:8])[CH2:19][CH2:18]1)=[O:24])([CH3:14])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: 60 °C

Procedure

To 1.26 g (8.37 mmol) 4-chloro-benzylcyanide was added bis-(2-chloroethyl)-carbamic acid tert-butyl ester (2.02 g, 8.37 mmol) in 25 ml N,N-dimethylformamide. The resulting mixture was stirred and cooled in an ice bath, then sodium hydride (60% suspension in mineral oil) (1.1 g, 42 mmol) was added portionwise. The reaction was brought to room temperature and then heated in an oil bath at 60° C. for 16 hours. The reaction mixture was quenched by addition of ice water and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed twice with water, once with brine, dried with magnesium sulfate and concentrated in vacuo. The residual brown oil was purified by silica gel chromatography eluting with hexane-ethyl acetate (9:1) to give the title compound (1.44 g, 54%).

Workup

temperaturecooled in an ice bath
customwas brought to room temperature
customThe reaction mixture was quenched by addition of ice water
extractionthe aqueous phase was extracted with ethyl acetate
washThe combined organic layers were washed twice with water, once with brine
dry with materialdried with magnesium sulfate
concentrationconcentrated in vacuo
customThe residual brown oil was purified by silica gel chromatography
washeluting with hexane-ethyl acetate (9:1)

Sources & evidence

ORD record: ord-17fc0604bf3848b487963cb4d3764664
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653096B2

Reaction notes

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