Lithium hydroxide, monohydrate → 3-((2-Tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoic acid

HRID 899463Notes

Reaction equation

HRID 899463 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:38])([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:21]=[C:22]([C:24]2([C:29]#[N:30])[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:23]=1)[C:16]([O:18]CC)=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C:9]([CH3:38])([CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:21]=[C:22]([C:24]2([C:29]#[N:30])[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:23]=1)[C:16]([OH:18])=[O:17])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 67319292Ethyl 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoate

Product 1

HCID 673191833-((2-Tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoate (0.13 g, 0.25 mmol) and LiOH.H2O (31 mg, 0.75 mmol) in 6.5 mL THF and 2.5 mL H2O was stirred at rt overnight. Additional LiOH.H2O (25 mg, 0.60 mmol) was added and the reaction was continued for 64 h. The mixture was concentrated, diluted with H2O, made acidic with 10% citric acid solution and extracted with EtOAc. The combined organic layers were washed with brine. Drying and solvent evaporation gave 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoic acid. 1H NMR (500 MHz, CDCl3) δ 8.09 (app d, J=1.5 Hz, 1H), 8.04 (s, 1H), 7.74 (s, 1H), 7.28-7.20 (m, 3H), 7.17 (m, 2H), 4.62 (s, 3H), 3.58 (bs, 1H), 3.48 (d, J=8.5 Hz, 1H), 3.15 (d, J=12.9 Hz, 1H), 2.95 (d, J=13.2 Hz, 1H), 2.54 (m, 2H), 2.14-1.96 (m, 6H), 1.47 (s, 9H), 1.28 (s, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with H2O
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. customDrying
  6. customsolvent evaporation

Sources & evidence

ORD record
ord-2a117f74145442efa7996667c25b9e43
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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