Lithium Hydroxide → (R)-4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoic acid

HRID 1771224Notes

Reaction equation

HRID 1771224 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]([O:32][P:33]([O:38][CH2:39][CH3:40])([O:35][CH2:36][CH3:37])=[O:34])[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.[OH-].[Li+]>C1COCC1.CO.O>[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]([O:32][P:33]([O:35][CH2:36][CH3:37])([O:38][CH2:39][CH3:40])=[O:34])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:31]=[CH:30][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 58080102(R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate2×

Product 1

HCID 58080188(R)-4-(4-((4'-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoic acidYield 86.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

A solution of (R)-ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(diethoxyphosphoryloxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 119, 500 mg, 0.85 mmol) in THF (10 ml) and MeOH (2.5 ml), at room temperature, was treated with a solution of lithium hydroxide (102 mg, 4.27 mmol) in water (2.5 ml). The reaction was heated to 30° C. overnight and subsequently warmed to 40° C. for about 5 hours. The mixture was allowed to cool to room temperature whereupon the volatiles were removed under reduced pressure. The concentrate was diluted with 30 ml of water, acidified with a few drops of 6N HCl to provide a white precipitate. The precipitate was collected by vacuum filtration to give the title compound (410 mg, yield: 86%).

Workup

  1. temperaturesubsequently warmed to 40° C. for about 5 hours
  2. temperatureto cool to room temperature whereupon the volatiles
  3. customwere removed under reduced pressure
  4. additionThe concentrate was diluted with 30 ml of water
  5. customto provide a white precipitate
  6. filtrationThe precipitate was collected by vacuum filtration

Sources & evidence

ORD record
ord-cf613b5570fd43848b9ca4d286b4e8f4
Source dataset
uspto-grants-2016_02
Patent number
US09248140B2

Reaction notes

Loading…