Methanesulfonamide → 5-Chloro-2-fluoro-4-methyl-N-(methylsulfonyl)benzamide

HRID 2048104Notes

Reaction equation

[Cl:1][C:2]1[C:3]([CH3:12])=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[CH3:13][S:14]([NH2:17])(=[O:16])=[O:15].Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[C:3]([CH3:12])=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:17][S:14]([CH3:13])(=[O:16])=[O:15])=[O:8]

Participants

Conditions

Temperature: 30 °C

Procedure

To 5-chloro-2-fluoro-4-methylbenzoic acid (Preparation 241, 200 g, 1.06 mol) in DCM (1.4 L) was added methanesulphonamide (152 g, 1.6 mol), 4-(dimethylamino)pyridine (183 g 1.6 mol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (306 g, 1.6 mol). The reaction mixture spontaneously heated at 30° C. over 30 minutes, then it was stirred at room temperature for 18 hours under a nitrogen atmosphere. The reaction mixture was washed with aqueous hydrochloric acid (4 M, 0.8 L). The organic layer was separated, washed with water (500 mL), dried over sodium sulphate and concentrated in vacuo to yield a tan solid, which was recrystallised from hot EtOAc (0.9 L) by addition of n-heptane (100 mL) and cooling to yield the title compound (118 g, 45%):

Workup

washThe reaction mixture was washed with aqueous hydrochloric acid (4 M, 0.8 L)
customThe organic layer was separated
washwashed with water (500 mL)
dry with materialdried over sodium sulphate
concentrationconcentrated in vacuo
customto yield a tan solid, which
customwas recrystallised from hot EtOAc (0.9 L) by addition of n-heptane (100 mL)
temperaturecooling

Sources & evidence

ORD record: ord-e4465144b8e04f8fb5b9a79c479edb63
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592629B2

Reaction notes

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