Reaktion #9694

Reaktionsgleichung

butyl (1R,2R)-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)-amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate

sodium hydroxide

→

(1R,2R)-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

Ausbeute 30.0%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was then removed by rotary evaporation
2. 2
   workup.ADDITIONWater (5 mL) was added to the residue
3. 3
   Extraktionthe mixture was extracted with ethyl acetate
4. 4
   workup.ADDITIONThe aqueous layer was then treated with 1 N aqueous HCl
5. 5
   Extraktionextracted with ethyl acetate
6. 6
   SonstigeThe organic phase was evaporated under reduced pressure
7. 7
   Sonstigethe residue was purified by flash chromatography (Biotage Flash 40S, 6:1 EtOAc/hexane)

Vorschrift

To a solution of butyl (1R,2R)-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)-amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate in methanol (8 mL) was added 1 N aqueous sodium hydroxide (6.15 mL), and the mixture was stirred at 50° C. overnight. The solvent was then removed by rotary evaporation. Water (5 mL) was added to the residue, and the mixture was extracted with ethyl acetate. The aqueous layer was then treated with 1 N aqueous HCl to adjust the acidity to pH 2, and then extracted with ethyl acetate. The organic phase was evaporated under reduced pressure, and the residue was purified by flash chromatography (Biotage Flash 40S, 6:1 EtOAc/hexane) to afford (1R,2R)-2-({3′-fluoro-4′-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid (129 mg, 30%, 89% ee). LC-MS ret. time 3.56 min, m/z 491.3 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.58–1.84 (m, 4H), 1.96–2.01 (m, 1H), 2.14–2.17 (m, 1H). 3.22 (q, 1H), 3.77 (s, 3H), 4.02–4.10 (q, 1H), 6.94 (dd, 1H), 7.46 (d, 1H), 7.53 (d, 1H), 7.65–7.76 (m, 2H), 7.86 (d, 2H), 8.04 (d, 2H), 8.72 (t, 1H), 10.33 (br s, 1H).

Quelle