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 907738Notes

Reaction equation

HRID 907738 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-6ee3de57d80a465ca7d1a915dd5a7138
Source dataset
uspto-grants-2011_09
Patent number
US08013166B2

Reaction notes

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