methyl 4-{(3S)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}-4-oxobutanoate → methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoate

HRID 603232Notes

Reaction equation

HRID 603232 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]([C:25](=O)[CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]>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]([O:30][CH3:31])=[O:29])[CH2:20]3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 1

HCID 57656799methyl 4-{(3S)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}-4-oxobutanoate

Product 2

HCID 222AmmoniaHCID 57656696methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoateYield 68.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl 4-{(3S)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}-4-oxobutanoate (240 mg) in tetrahydrofuran (5 mL) at room temperature under argon was added a 1M solution of BH3 in THF (1 mL). The solution was heated to reflux temperature for 1 hour and then cooled to ambient temperature. The reaction was quenched with methanol and then concentrated at reduced pressure. To the residue was added saturated HCl in methanol (10 mL) and the mixture was heated to reflux temperature for 1 hour and then cooled to ambient temperature. The mixture was stirred at ambient temperature overnight and then concentrated at reduced pressure. 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 methyl 4-{(3R)-3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)methyl]piperidin-1-yl}butanoate (80 mg, 34%).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux temperature for 1 hour
  3. customThe reaction was quenched with methanol
  4. concentrationconcentrated at reduced pressure
  5. additionTo the residue was added saturated HCl in methanol (10 mL)
  6. temperaturethe mixture was heated
  7. temperatureto reflux temperature for 1 hour
  8. temperaturecooled to ambient temperature
  9. concentrationconcentrated at reduced pressure
  10. customThe residue was purified
  11. washeluting with a mixture of 5-95% acetonitrile in water
  12. washSCX-2 column eluting with methanol

Sources & evidence

ORD record
ord-99951566c1f947fe80661d04e6b1e6ce
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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