Lithium Hydroxide → 4-Chloro-3'-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)-methyl)biphenyl-3-carboxylic acid

HRID 404957Notes

Reaction equation

HRID 404957 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C:21](=[O:25])[N:20]([CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:19]4)[CH:9]=2)=[CH:4][C:3]=1[C:31]([O:33]C)=[O:32].[Li+].[OH-]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C:21](=[O:25])[N:20]([CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:19]4)[CH:9]=2)=[CH:4][C:3]=1[C:31]([OH:33])=[O:32]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 50993811Methyl 4-chloro-3'-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)biphenyl-3-carboxylate

Product 1

HCID 461827454-Chloro-3'-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)-methyl)biphenyl-3-carboxylic acidYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Crude methyl 4-chloro-3′-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)biphenyl-3-carboxylate (109 mg, 0.23 mmol) was dissolved in tetrahydrofuran (17 mL) and 2M LiOH (0.57 mL, 1.15 mmol) was added and the mixture was heated at reflux for 3 h. The solvent was evaporated and the residue was dissolved in water and neutralized using 2M HCl. The aqueous layer was extracted with ethyl acetate and the organic layer was dried over anhydrous Na2SO4. The solvent was evaporated in vacuo to obtain the crude acid as a yellow solid. The crude residue was purified using automated prep-HPLC to yield the desired compound (48 mg, 46%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.78 (d, J=8.5 Hz, 1H), 7.65-7.41 (m, 6H), 7.05 (d, J=8.5 Hz, 1H), 6.99 (s, 1H), 5.16 (s, 2H), 4.74 (m, 1H), 4.30 (s, 2H), 1.97 (m, 2H), 1.76-1.59 (m, 6H). HRMS: calcd. for C27H24CINO4 [M+H]+ 462.1467; found 462.1468.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 3 h
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in water
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried over anhydrous Na2SO4
  7. customThe solvent was evaporated in vacuo
  8. customto obtain the crude acid as a yellow solid
  9. customThe crude residue was purified

Sources & evidence

ORD record
ord-6e189ef05af04f62bd66b98f58ae05cc
Source dataset
uspto-grants-2014_06
Patent number
US08748632B2

Reaction notes

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