Lithium Hydroxide → 4-{(3R)-3-[(4-{[(3,4-Dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoic acid

HRID 603231Notes

Reaction equation

HRID 603231 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][CH2:27][C:28]([O:30]C)=[O:29])[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[OH-].[Li+]>O1CCCC1>[NH3:9].[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][CH2:27][C:28]([OH:30])=[O:29])[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 57656696methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoate

Product 2

HCID 222AmmoniaHCID 576566474-{(3R)-3-[(4-{[(3,4-Dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoic acidYield 154.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoate (80 mg) in tetrahydrofuran (5 mL) was added 1M aqueous lithium hydroxide (1 mL). The mixture was stirred overnight at room temperature. The mixture was then loaded directly onto an SCX-2 column and eluted with methanol then 7M NH3 in methanol. The basic fraction was concentrated at reduced pressure and the residue was purified using reverse phase HPLC eluting with a mixture of 5-95% acetonitrile in water and then SCX-2 column eluting with methanol then 7M NH3 in methanol to give the title compound as a white solid (60 mg, 77%).

Workup

  1. washeluted with methanol
  2. concentrationThe basic fraction was concentrated at reduced pressure
  3. customthe residue was purified
  4. washeluting with a mixture of 5-95% acetonitrile in water
  5. washSCX-2 column eluting with methanol

Sources & evidence

ORD record
ord-d479d75dea7946e88a25c3004e1f7518
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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