Phosgene → 1,1-Dimethylethyl 4-(6-methoxy-5-chloro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 2064154Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]1.[C:25](Cl)(Cl)=[O:26].C(N(CC)CC)C>ClCCl>[CH3:10][O:9][C:5]1[C:6]([Cl:8])=[CH:7][C:2]2[NH:1][C:25](=[O:26])[N:11]([CH:12]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]3)[C:3]=2[CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1,1-Dimethylethyl 4-[(2-amino-4-chloro-5-methoxyphenyl)amino]-1-piperidinecarboxylate (D48) (280 mg) was dissolved in 5 ml of dichloromethane at 0° C. and phosgene (20% in toluene, 0.5 ml) and triethylamine (0.3 ml) were added and the mixture was stirred at 0° C. for 1 h, then washed with aqueous citric acid, then water, dried over MgSO4, filtered and evaporated The product was chromatographed on silica gel eluting with methanol-dichloromethane mixtures, crystallised from diethyl ether, and then further purified by MDAP to yield the title compound, 40 mg.

Workup

washwashed with aqueous citric acid
dry with materialwater, dried over MgSO4
filtrationfiltered
customevaporated The product
customwas chromatographed on silica gel eluting with methanol-dichloromethane mixtures
customcrystallised from diethyl ether
customfurther purified by MDAP

Sources & evidence

ORD record: ord-ec2510fec2ae4fb78c8cdef84282ef89
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288412B2

Reaction notes

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