Chlorosulfonic acid → 5-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-sulfonyl chloride
Reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([NH:12][C:13](=[O:15])[CH3:14])[S:5][C:6]=1[C:7]1[S:8][CH:9]=[CH:10][CH:11]=1.[Cl:16][S:17](O)(=[O:19])=[O:18].P(Cl)(Cl)(Cl)(Cl)Cl.[Cl-].[P+]=O>C(Cl)Cl>[C:13]([NH:12][C:4]1[S:5][C:6]([C:7]2[S:8][C:9]([S:17]([Cl:16])(=[O:19])=[O:18])=[CH:10][CH:11]=2)=[C:2]([CH3:1])[N:3]=1)(=[O:15])[CH3:14]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
N-[4-methyl-5-(2-thienyl)-1,3-thiazol-2-yl]acetamide, prepared in Step I (500 mg; 2.10 mmol; 1 eq.) is dissolved in DCM (30 ml). The reaction mixture is cooled down to 0° C. and chlorosulfonic acid (0.70 ml; 10.49 mmol; 5 eq.) dissolved in DCM (30 ml) is added dropwise over 15 min. The solution becomes pink. It is stirred 15 minutes at 0° C. Phosphorus pentachloride (873.7 mg; 4.20 mmol; 2 eq.) and phosphorus oxide chloride (0.78 ml; 8.39 mmol; 4 eq.) are added successively. The reaction mixture is stirred for 2 additional hours at room temperature. It is poured on ice and the desired product is extracted with 2 portions of EtOAc, dried over MgSO4, and evaporated, affording 5-[2-(acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-sulfonyl chloride as yellow solid (650 mg; 92%). M− (ESI): 335.08; M+ (ESI): 337.08.
Workup
- additionis added dropwise over 15 min
- stirringThe reaction mixture is stirred for 2 additional hours at room temperature
- additionIt is poured on ice
- extractionthe desired product is extracted with 2 portions of EtOAc
- dry with materialdried over MgSO4
- customevaporated
Sources & evidence
- ORD record
- ord-0d4311687ffc464d823a761a37d32881
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08399497B2
Reaction notes
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