Dimethylamine, hydrochloride → 4-Dimethylamino-3-methanesulfonyl-benzoic acid methyl ester

HRID 1041867Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7](F)=[C:6]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:5]=1.Cl.[CH3:17][NH:18][CH3:19].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:9]=[CH:8][C:7]([N:18]([CH3:19])[CH3:17])=[C:6]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:5]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of 5.23 g (22.5 mmol) 4-Fluoro-3-methanesulfonyl-benzoic acid methyl ester (J. Med. Chem.; 40; 13; 1997; 2017-2034) and 60.0 ml dimethylsulphoxid were added 2.23 g (27.0 mmol) dimethylamine hydrochloride and 6.54 g (47.3 mmol) potassium carbonate. The reaction mixture was stirred for 7 h at 60° C. in an autoclave and was concentrated with high vacuum rotation evaporator at 65° C. The residue was diluted with dichloromethane, washed twice with water. The combined water phases were extracted with dichloromethane. The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The oily crude was purified by column chromatography and the desired product 10a was obtained in 56% yield (3.24 g, 12.6 mmol).

Workup

concentrationwas concentrated with high vacuum rotation evaporator at 65° C
additionThe residue was diluted with dichloromethane
washwashed twice with water
extractionThe combined water phases were extracted with dichloromethane
washThe combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution
dry with materialdried with sodium sulphate
concentrationconcentrated
customThe oily crude was purified by column chromatography

Sources & evidence

ORD record: ord-4e90e05250034a908ee44c51913f701b
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08557776B2

Reaction notes

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