Reaktion #9709

Reaktionsgleichung

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

Ausbeute 43.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was then evaporated to dryness under reduced pressure
2. 2
   EinengenThe reaction mixture was concentrated under reduced pressure
3. 3
   workup.ADDITIONConc. HCl was added
4. 4
   Extraktionthe mixture was extracted with EtOAc
5. 5
   WaschenThe combined organic phases were washed with brine
6. 6
   Trocknendried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated
9. 9
   Filtrationthe precipitate was collected by filtration
10. 10
    Waschenwashed with MeOH, EtOAc, and DCM
11. 11
    Sonstigedried in a vacuum oven

Vorschrift

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).

Quelle