Lithium Hydroxide → (S)-4-(4-((4'-Chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid

HRID 1771201Notes

Reaction equation

HRID 1771201 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@@H:14]([OH:32])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1.[Li+].[OH-]>C1COCC1.CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C@@H:14]([OH:32])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:30][CH:31]=3)[CH2:17][CH2:16]2)=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 56650672(S)-Ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate2×

Product 1

HCID 58080142(S)-4-(4-((4'-Chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-Ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 11B, 150.0 mg, 0.33 mmol) was dissolved in THF (6.0 ml) and methanol (1.4 ml). A solution of LiOH (40.6 mg) in water (1.4 ml) was added. The solution was heated at 500 overnight. The reaction mixture was allowed to cool to room temperature and then concentrated under reduced pressure. The residue was diluted with water (5 ml), acidified with 1N aq. HCl (2.0 ml), and extracted with DCM (2×5 ml). The extract was dried (MgSO4), filtered through cotton, and evaporated under vacuum to provide the title product as a substantially separated enantiomer (155 mg, yield: almost quantitative) 1H NMR (400 MHz, DICHLOROMETHANE-d2) δ ppm 0.79-0.94 (m, 1H) 0.98-1.12 (m, 1H) 1.14-1.40 (m, 4H) 2.04 (m, 1H) 2.67 (td, J=12.51, 2.78 Hz, 1H) 2.78 (td, 1H) 3.74 (d, 1H) 3.91 (m, 1H) 4.48 (d, 1H) 6.81 (d, 2H) 7.17-7.29 (m, 3H) 7.31-7.49 (m, 4H) 7.61 (dd, 1H) 7.84-7.93 (m, 2H).

Workup

  1. temperatureThe solution was heated at 500 overnight
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with water (5 ml)
  4. extractionextracted with DCM (2×5 ml)
  5. dry with materialThe extract was dried (MgSO4)
  6. filtrationfiltered through cotton
  7. customevaporated under vacuum

Sources & evidence

ORD record
ord-13a72434d4ac44f38f4a79a7ed1e058e
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

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