Réaction #59208

Équation de réaction

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

Rendement 43.0%

Conditions de réaction

Traitement

1. 1
   AutreThe mixture was then evaporated to dryness under reduced pressure
2. 2
   ConcentrationThe reaction mixture was concentrated under reduced pressure
3. 3
   workup.ADDITIONConc. HCl was added
4. 4
   Extractionthe mixture was extracted with EtOAc
5. 5
   LavageThe combined organic phases were washed with brine
6. 6
   Séchagedried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated
9. 9
   Filtrationthe precipitate was collected by filtration
10. 10
    Lavagewashed with MeOH, EtOAc, and DCM
11. 11
    Autredried in a vacuum oven

Mode opératoire

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).

Source