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

HRID 9598Notes

Reaction equation

HRID 9598 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([C@@H:28]3[CH2:32][CH2:31][CH2:30][C@H:29]3[C:33]([O:35]CCCC)=[O:34])=[O:27])=[CH:22][CH:21]=2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:12]=2[N:13]=1.[OH-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([C@@H:28]3[CH2:32][CH2:31][CH2:30][C@H:29]3[C:33]([OH:35])=[O:34])=[O:27])=[CH:22][CH:21]=2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[S:10][C:11]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58681321butyl (1R,2R)-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-2-yl)-amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate

Product 1

HCID 11248860(1R,2R)-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acidYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

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).

Workup

  1. customThe solvent was then removed by rotary evaporation
  2. additionWater (5 mL) was added to the residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. additionThe aqueous layer was then treated with 1 N aqueous HCl
  5. extractionextracted with ethyl acetate
  6. customThe organic phase was evaporated under reduced pressure
  7. customthe residue was purified by flash chromatography (Biotage Flash 40S, 6:1 EtOAc/hexane)

Sources & evidence

ORD record
ord-9127b4d7ff9c4ca1a75f65c8ee03a551
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

Loading…