Реакция #9709

Уравнение реакции

NaOH

racemic methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclobutane-carboxylate

2-chloro-4,6-difluoro-1,3-benzothiazole

n-butanol

→

racemic trans-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1-biphenyl-4-yl}-carbonyl)cyclopentanecarboxylic acid

Выход 43.0%

Условия реакции

Обработка

1. 1
   ДругоеThe mixture was then evaporated to dryness under reduced pressure
2. 2
   КонцентрированиеThe reaction mixture was concentrated under reduced pressure
3. 3
   workup.ADDITIONConc. HCl was added
4. 4
   Экстракцияthe mixture was extracted with EtOAc
5. 5
   ПромывкаThe combined organic phases were washed with brine
6. 6
   Сушкаdried over sodium sulfate
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated
9. 9
   Фильтрацияthe precipitate was collected by filtration
10. 10
    Промывкаwashed with MeOH, EtOAc, and DCM
11. 11
    Другоеdried in a vacuum oven

Методика

To a solution of racemic methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclobutane-carboxylate (250 mg, 0.77 mmol) in n-butanol (15 mL) was added 2-chloro-4,6-difluoro-1,3-benzothiazole (318 mg, 1.55 mmol), and the resulting solution was heated at 90° C. overnight. The mixture was then evaporated to dryness under reduced pressure, and the residue was brought up in MeOH. Then 1 N aqueous NaOH (8.0 mL, 8.0 mmol) was added to the suspension, and the reaction mixture was stirred at 50° C. overnight. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in water. Conc. HCl was added to adjust the acidity to pH 1, and the mixture was extracted with EtOAc. The combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was brought up in MeOH, and the precipitate was collected by filtration, washed with MeOH, EtOAc, and DCM, and dried in a vacuum oven to afford racemic trans-2-({4′-[(4,6-difluoro-1,3-benzothiazol-2-yl)amino]-1,1-biphenyl-4-yl}-carbonyl)cyclopentanecarboxylic acid (160 mg, 43%). LC-MS ret. time 4.12; m/z 479.3 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 1.55–1.86 (m, 4H), 2.00 (m, 1H), 2.18 (m, 1H), 3.22 (q, 1H), 4.01 (q, 1H), 7.28 (m, 1H), 7.65 (m, 1H), 7.82 (m, 4H), 7.88 (d, 2H), 8.05 (d, 2H), 10.83(s, 1H), 12.23 (s, 1H).

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