Sodium Hydroxide → (1R,2R)-2-{[4'-(1H-benzimidazol-2-ylamino)-3'-fluoro-1,1'-biphenyl-4-yl]carbonyl}-cyclopentanecarboxylic acid

HRID 30935Notes

Reaction equation

HRID 30935 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([C@@H:25]3[CH2:29][CH2:28][CH2:27][C@H:26]3[C:30]([O:32]C)=[O:31])=[O:24])=[CH:19][CH:18]=2)=[CH:13][C:12]=1[F:34].[OH-].[Na+]>CO.C1COCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([C@@H:25]3[CH2:29][CH2:28][CH2:27][C@H:26]3[C:30]([OH:32])=[O:31])=[O:24])=[CH:19][CH:18]=2)=[CH:13][C:12]=1[F:34]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 58681304HCID 58681304, compound

Product 1

HCID 11442118(1R,2R)-2-{[4'-(1H-benzimidazol-2-ylamino)-3'-fluoro-1,1'-biphenyl-4-yl]carbonyl}-cyclopentanecarboxylic acidYield 31%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl (1R,2R)-2-{[4′-(1H-benzimidazol-2-ylamino)-3′-fluoro-1,1′-biphenyl-4-yl]-carbonyl}cyclopentanecarboxylate (100 mg, 0.22 mmol) was dissolved in methanol and treated with an excess of 1 N aqueous sodium hydroxide solution (2.19 mL, 2.19 mmol). The solution was stirred at rt for 1 h, and then was concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate, and the aqueous layer was adjusted to pH 2 by the addition of 1 N aqueous HCl. The organic layer was separated, washed with brine, dried (MgSO4), and concentrated under reduced pressure to provide an orange oil. The oil was suspended in THF and stirred until a precipitate formed. The precipitate was collected by filtration and washed with additional THF to provide the title compound as a yellow solid (30 mg, 31%, 80% ee). 1H NMR (300 MHz, DMSO-d6) δ 13.12 (br s, 1H), 11.30 (br s, 1H), 8.12 (d, 2H), 7.96-7.76 (m, 5H), 7.46-7.42 (m, 2H), 7.30-7.26 (m, 2H), 4.15-4.07 (m, 1H), 3.27-3.19 (m, 1H), 2.21-2.12 (m, 1H), 2.05-1.96 (m, 1H), 1.86-1.55 (m, 4H); LC-MS m/z 444.4 (MH+), retention time 2.79 minutes.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customThe residue was partitioned between water and ethyl acetate
  3. additionthe aqueous layer was adjusted to pH 2 by the addition of 1 N aqueous HCl
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customto provide an orange oil
  9. stirringstirred until a precipitate
  10. customformed
  11. filtrationThe precipitate was collected by filtration
  12. washwashed with additional THF

Sources & evidence

ORD record
ord-f79f32a17c574cf59c2c53ce9a3f5d13
Source dataset
uspto-grants-2008_09
Patent number
US07423156B2

Reaction notes

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