Water → HCID 19973055, compound

Temperature

78 °C

A solution of p-thiocresol (4.94 g, 39.8 mmol), triethylamine (5.55 mL, 39.8 mmol) in dichloromethane (30 mL) was added dropwise over 12 minutes to a solution of 2,3-dichlorothiophene-5-sulfonyl chloride (5.0 g, 19.9 mmol) in dichloromethane (50 mL) at -78° C. under a dry nitrogen atmosphere. An additional 10 mL of dichloromethane was added and the reaction mixture was stirred at-78° C. for 2 h and then warmed to room temperature over 20 minutes. The reaction mixture was poured into water (400 mL) and the layers were separated. The dichloromethane phase was washed with water (2×200 mL) and the combined aqueous phase was acidified with concentrated HCl. Solid NaCl was also added to the aqueous phase which was then extracted with ether (4×200 mL). The extracts were combined and dried (Na25SO4) and concentrated to afford 2,3-dichlorothiophene-5-sulfinic acid as a white solid (2.89 g, 67%): NMR (DMSO, d 6): δ 9.1 (broad s, 1H, O H), 7.54 (s, 1H, thiophene H); MS(EI): 216, 218, 220 (70, 50, 10%, MI), 199, 201, 203 (60, 50, 10%,--OH), 169 (50%), 167 (70%), 154 (70%), 152 (100%).This ulfinic acid (2.33 g, 10.73 mmol) was dissolved in a solution of sodium hydroxide (0.42 g, 10.73 mmol) in methanol (25 mL) at room temperature. The methanol was removed and residual water was removed by azeotroping with benzene to provide 2,3-dichlorothiophene-5-sulfinic acid, sodium salt of formula (IV) as a whir solid (2.57 g, 100%): NMR (DMSO, d6): δ 6.89 (s, 1H, thiophene H); Anal. Calc. for C4HCl2O2S2 : C, 20.09; H, 0.41; Found: C, 19.80; H, 0.52. This sulfinic acid, sodium salt of formula (IV) (2.12 g, 8.87 mmol) was mixed with 5-bromo-thiazolidine-2,4-dione (1.58 g, 8.06 mmol) and Aliquat 336 (tricaprylylmethylammonium chloride, 0.45 mL) and allowed to stand overnight. Dilute aqueous HCl (100 mL) was added and the aqueous reaction mixture was extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine and concentrated. The crude product was purified by flash chromatography using acid washed (2% H3PO4 in methanol) silica gel and 82:18 ethyl acetate: petroleum ether as eluant to provide the title compound of formula (V) as a white solid: mp 176°-177° C: NMR (DMSO, d 6): δ 13.0 (broad s, 1H,N H), 8.10 (s, 1H, thiophene H); 6.85 (s, 1H, C H); MS(E1): 331,333, 335 (30, 20, 5%, MI), 215, 217, 219 (100, 70, 15%); Anal. Calc. for C7H3Cl2NO4S3 : C, 25.31; H, 0.91; N, 4.22; Found: C, 25.83; H, 1.00; N, 4.23.

1. temperaturewarmed to room temperature over 20 minutes
2. customthe layers were separated
3. washThe dichloromethane phase was washed with water (2×200 mL)
4. additionSolid NaCl was also added to the aqueous phase which
5. extractionwas then extracted with ether (4×200 mL)
6. customdried (Na25SO4)
7. concentrationconcentrated

ORD record

ord-463e27527d914995ade2e9c98df8339e

Source dataset

uspto-grants-1996_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05574051