Chlorosulfonic acid → 4-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]-5-bromothiophene-2-sulfonylchloride

HRID 1360874Notes

Reaction equation

[Br:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[C:7]1[S:11][C:10]([NH:12][C:13](=[O:15])[CH3:14])=[N:9][C:8]=1[CH3:16].[Cl:17][S:18](O)(=[O:20])=[O:19].P(Cl)(Cl)(Cl)(Cl)Cl.[Cl-].[P+]=O>C(Cl)Cl>[C:13]([NH:12][C:10]1[S:11][C:7]([C:6]2[CH:5]=[C:4]([S:18]([Cl:17])(=[O:20])=[O:19])[S:3][C:2]=2[Br:1])=[C:8]([CH3:16])[N:9]=1)(=[O:15])[CH3:14]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of N-[5-(2-bromo-thiophen-3-yl)-4-methyl-thiazol-2-yl]-acetamide obtained in Step II, as describe above (1100 mg; 3.47 mmol; 1 eq), in DCM (60 ml) is cooled to 0° C. with an ice bath. The reaction is degassed with nitrogen and chlorosulfonic acid (1.16 ml; 17.3 mmol; 5 eq) dissolved in DCM (30 ml) is added dropwise. The reaction mixture is stirred at 0° C. for 15 minutes. Phosphorus pentachloride (1444 mg; 6.94 mmol; 2 eq) is added followed directly by phosphorus oxide chloride (1.3 ml; 13.9 mmol; 4 eq). The reaction is stirred for an additional 2 hours at room temperature. Then the reaction mixture is poured into a beaker with crushed ice and directly transferred in a separated funnel. It is extracted with 2 portions EtOAc. The organic layer is dried over MgSO4, affording the title compound (1440 mg; quantitative yield).

Workup

additionis added dropwise
stirringThe reaction is stirred for an additional 2 hours at room temperature
additionThen the reaction mixture is poured into a beaker with crushed ice
customdirectly transferred in a separated funnel
extractionIt is extracted with 2 portions EtOAc
dry with materialThe organic layer is dried over MgSO4

Sources & evidence

ORD record: ord-59b7ab109d404748860a7fcd085ddc74
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879888B2

Reaction notes

Loading…