Реакция #10817

Уравнение реакции

N-(4-acetyl-phenyl)-methanesulfonamide

2-(4-formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid

lithium methoxide

→

title compound

Выход 15.5%

2-{4-[3-(4-Methanesulfonylamino-phenyl)-3-oxo-E-propenyl]-5-methoxy-2-thiophen-2-yl-phenoxy}-2-methyl-propionic acid

Выход 15.5%

Растворители

water

DMF

MeOH

Условия реакции

Обработка

1. 1
   Экстракцияwas then extracted with isopropyl acetate (2×50 mL)
2. 2
   ДругоеThe aqueous portion was collected
3. 3
   ЭкстракцияThe aqueous solution was then extracted with isopropyl acetate (2×50 mL)
4. 4
   ДругоеThe organic was collected
5. 5
   Сушкаdried over sodium sulfate
6. 6
   Концентрированиеconcentrated to a green solid
7. 7
   ДругоеAttempted to recrystallize crude material from ethanol/hexanes
8. 8
   Концентрированиеhowever, this mixture was concentrated
9. 9
   workup.STIRRINGstirred with ethyl acetate (3 mL)

Методика

A solution of N-(4-acetyl-phenyl)-methanesulfonamide (Ex-100A, 279.6 mg, 1.31 mmol) and 2-(4-formyl-5-methoxy-2-thiophen-2-yl-phenoxy)-2-methyl-propionic acid (Ex-47D, 400 mg, 1.20 mmol) in DMF (5.25 mL) and MeOH (2.25 mL) was treated with lithium methoxide (182.2 mg, 4.8 mmol) and stirred for 5 hours at room temp. under nitrogen atmosphere. The reaction mixture was diluted with water (25 mL) which was then extracted with isopropyl acetate (2×50 mL). The aqueous portion was collected and acidified to a pH of 3 with 3N HCl. The aqueous solution was then extracted with isopropyl acetate (2×50 mL). The organic was collected, dried over sodium sulfate, and concentrated to a green solid. Attempted to recrystallize crude material from ethanol/hexanes; however, this mixture was concentrated and stirred with ethyl acetate (3 mL) to give 95.6 mg (14%) of the title compound as a yellow solid, mp 181–183° C. 1H-NMR (DMSO-d6) δ 10.31 (br s, 1H), 8.24 (s, 1H), 8.12 (d, 2H), 7.95 (d, 1H), 7.87 (d, 1H), 7.67 (d, 1H), 7.50 (d, 1H), 7.30 (d, 2H), 7.09 (t, 1H), 6.45 (s, 1H), 3.81 (s, 3H), 3.08 (s, 3H), 1.65 (s, 6H). MS m/z=516 ([M+H]+, 100%). HRMS m/z: calc. 516.1150, found 516.1165.

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