Dichloromethane → N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-(1,3-dithian-2-yl)thiophene-3-sulfonamide

HRID 2047263Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2047263
[Cl:1][C:2]1[C:3]([CH3:18])=[N:4][O:5][C:6]=1[NH:7][S:8]([C:11]1[CH:15]=[CH:14][S:13][C:12]=1[CH:16]=O)(=[O:10])=[O:9].ClCCl.B(F)(F)F.CCOCC.[CH2:31]([SH:35])[CH2:32][CH2:33][SH:34]>O>[Cl:1][C:2]1[C:3]([CH3:18])=[N:4][O:5][C:6]=1[NH:7][S:8]([C:11]1[CH:15]=[CH:14][S:13][C:12]=1[CH:16]1[S:35][CH2:31][CH2:32][CH2:33][S:34]1)(=[O:10])=[O:9]

Komponenten

6

Edukt 4

HCID 6344DichloromethaneHCID 8000Boron trifluoride etherateHCID 80131,3-PropanedithiolHCID 86691256N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-formylthiophene-3-sulfonamide

Produkt 1

HCID 86691255N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-(1,3-dithian-2-yl)thiophene-3-sulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a mixture of N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-formylthiophene-3-sulfonamide described in Production Example 1-3 (4.9 g, 16 mmol) and dichloromethane (100 mL) was successively added boron trifluoride diethyl etherate (8.1 mL, 64 mmol) and 1,3-propanedithiol (1.9 mL, 19 mmol) under ice cooling, followed by stirring at room temperature for 90 minutes. Water was added under ice cooling to the reaction mixture, which was then extracted with dichloromethane. The organic layer was washed with brine, and the solvent was distilled away under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to give N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-(1,3-dithian-2-yl)thiophene-3-sulfonamide as a crude product. To a mixture of crude N-(4-chloro-3-methyl-1,2-oxazol-5-yl)-2-(1,3-dithian-2-yl)thiophene-3-sulfonamide and tetrahydrofuran (50 mL) was added dropwise n-butyl lithium (9.7 mL, 16 mmol, 1.6 M n-hexane solution) at −78° C., followed by stirring for 20 minutes at an internal temperature of −35° C. The reaction mixture was cooled to −78° C., and 5-(chloromethyl)-6-methyl-1,3-dihydro-2-benzofuran described in Production Example 1-6 (960 mg, 5.3 mmol) was added at that temperature and stirred for 1 hour at 0° C. The reaction mixture was cooled to −78° C., and a mixture of acetic acid (0.90 mL, 16 mmol) and tetrahydrofuran (7 mL) was added at that temperature. The reaction mixture was gradually returned to room temperature, water and an aqueous citric acid solution were added at that temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and the solvent was distilled away under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=4:1) to give the title compound (1.6 g, 54% yield).

Aufarbeitung

  1. extractionwas then extracted with dichloromethane
  2. washThe organic layer was washed with brine
  3. distillationthe solvent was distilled away under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-2c10a8039b5c427aa53aed688c0fbee1
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08592470B2

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