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

HRID 512047Notes

Reaction equation

HRID 512047 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

6

Reactant 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 580424465-Chloro-2-fluoro-4-methylbenzoic acid

Product 1

HCID 580423685-Chloro-2-fluoro-4-methyl-N-(methylsulfonyl)benzamideYield 45%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-2-fluoro-4-methylbenzoic acid (Preparation 21, 200 g, 1.06 mol) in DCM (1.4 L) were 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). An exotherm of 30° C. was observed in the first 30 minutes, then the mixture 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) and dried over sodium sulfate to yield a tan solid, which was recrystallised from hot EtOAc (0.9 L) by addition of n-heptane (100 mL) and cooling to afford the title compound (118 g, 45%).

Workup

  1. customAn exotherm of 30° C.
  2. customwas observed in the first 30 minutes
  3. washThe reaction mixture was washed with aqueous hydrochloric acid (4 M, 0.8 L)
  4. customThe organic layer was separated
  5. washwashed with water (500 mL)
  6. dry with materialdried over sodium sulfate
  7. customto yield a tan solid, which
  8. customwas recrystallised from hot EtOAc (0.9 L) by addition of n-heptane (100 mL)
  9. temperaturecooling

Sources & evidence

ORD record
ord-1966949c10b645d8b589eedfdcda0f2a
Source dataset
uspto-grants-2015_08
Patent number
US09102621B2

Reaction notes

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