Methanol → (R)-5-(3-Hydroxypyrrolidine-1-carbonyl)-4'-methylbiphenyl-3-carboxylic acid

HRID 1845214Notes

Reaction equation

HRID 1845214 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([C:9]2[CH:10]=[C:11]([C:22]([O:24]CC)=[O:23])[CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)[CH:14]=2)=[O:8])[CH2:3]1.[OH-].[Li+].CO>O>[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([C:9]2[CH:10]=[C:11]([C:22]([OH:24])=[O:23])[CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)[CH:14]=2)=[O:8])[CH2:3]1

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 58188314(R)-Ethyl 5-(3-hydroxypyrrolidine-1-carbonyl)-4'-methylbiphenyl-3-carboxylate

Product 1

HCID 58188273(R)-5-(3-Hydroxypyrrolidine-1-carbonyl)-4'-methylbiphenyl-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of (R)-ethyl 5-(3-hydroxypyrrolidine-1-carbonyl)-4′-methylbiphenyl-3-carboxylate (1.25 g, 3.54 mmol), lithium hydroxide (0.42 g, 18 mmol), methanol (50 mL), and water (5 mL) was stirred at rt for 4 h. LC-MS indicated completion of the reaction. The volatiles were removed in vacuo and the residue was treated with water and acidified with 1N aq. HCl to pH 2-3 and extracted with EtOAc (50 mL×3). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to afford a white foam. LC-MS: 326.3 [M+1]+; 1H NMR (400 MHz, CD3OD): 8.33 (m, 1H), 8.11 and 8.10 (t, 1H, J=1.6 Hz), 7.98 and 7.97 (t, 1H, J=1.6 Hz), 7.57 (d, 2H, J=7.6 Hz), 7.30 (d, 2H, J=8.0 Hz), 4.51 and 4.38 (m, 1H), 3.85-3.35 (m, 4H), 2.39 (s, 3H), 2.20-1.90 (m, 2H).

Workup

  1. customcompletion of the reaction
  2. customThe volatiles were removed in vacuo
  3. additionthe residue was treated with water
  4. extractionextracted with EtOAc (50 mL×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto afford a white foam

Sources & evidence

ORD record
ord-2c92d888c2e84221a5b46c70e362f636
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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