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 2427379Notes

Reaction equation

HRID 2427379 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-e98a1518e9b2491095d48221fde94bbf
Source dataset
uspto-grants-2011_06
Patent number
US07968576B2

Reaction notes

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