反応 #59208

反応方程式

NaOH

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

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

収率 43.0%

反応条件

後処理

1. 1
   その他The mixture was then evaporated to dryness under reduced pressure
2. 2
   濃縮The reaction mixture was concentrated under reduced pressure
3. 3
   workup.ADDITIONConc. HCl was added
4. 4
   抽出the mixture was extracted with EtOAc
5. 5
   洗浄The combined organic phases were washed with brine
6. 6
   乾燥dried over sodium sulfate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated
9. 9
   ろ過the precipitate was collected by filtration
10. 10
    洗浄washed with MeOH, EtOAc, and DCM
11. 11
    その他dried in a vacuum oven

実験手順

To a solution of racemic methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclobutanecarboxylate (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).

出典