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

HRID 2405993Notes

Reaction equation

[H-].[Na+].[C:3]([O:7][C:8](=[O:16])[N:9]([CH2:13][CH2:14]Cl)[CH2:10][CH2:11]Cl)([CH3:6])([CH3:5])[CH3:4].[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([CH2:22][C:23]#[N:24])=[CH:20][CH:19]=1>CN(C)C=O>[C:3]([O:7][C:8]([N:9]1[CH2:13][CH2:14][C:22]([C:21]2[CH:25]=[CH:26][C:18]([Cl:17])=[CH:19][CH:20]=2)([C:23]#[N:24])[CH2:11][CH2:10]1)=[O:16])([CH3:6])([CH3:5])[CH3:4]

Participants

Conditions

Temperature: 65 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 2.9 g, 72.3 mmol) was added in small portions, over a period of 1 hour, to a solution of bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (6.74 g, 28 mmol) and 4-chlorobenzyl cyanide (3.8 g, 25 mmol) in anhydrous dimethylformamide (25 ml). The reaction mixture was heated at 65° C. for 1 hour and then stirred at room temperature for 89 hours. After this period, the reaction mixture was poured into ice/water (60 ml) and extracted with ethyl acetate (2×100 ml). The combined organic layers were washed with water and brine, dried, filtered and concentrated. Flash column chromatography on silica, eluting with hexane/dichloromethane/ethyl acetate (8:1:1), gave 4-(4-chlorophenyl)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (5.6 g, 17.5 mmol, 70%) as a white solid. LC-MS (LCT) m/z 320 [M+], Rt 7.71 min.

Workup

waitAfter this period
extractionextracted with ethyl acetate (2×100 ml)
washThe combined organic layers were washed with water and brine
customdried
filtrationfiltered
concentrationconcentrated
washFlash column chromatography on silica, eluting with hexane/dichloromethane/ethyl acetate (8:1:1)

Sources & evidence

ORD record: ord-503f660310374a53bb6d2699743ade17
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809336B2

Reaction notes

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