Ethanol → (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one oxalate

HRID 341318Notes

Reaction equation

HRID 341318 reaction equation
C(O)C.C([N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:21])[C@@H:18]([OH:20])[CH3:19])[CH2:13][CH2:12]1)C1C=CC=CC=1.C1CCCCC=1.O.O.[C:30]([OH:35])(=[O:34])[C:31]([OH:33])=[O:32]>O1CCCC1.[Pd]>[C:30]([OH:35])(=[O:34])[C:31]([OH:33])=[O:32].[OH:20][C@@H:18]([CH3:19])[C:17]([N:14]1[CH2:13][CH2:12][NH:11][CH2:16][CH2:15]1)=[O:21]

Participants

7

Reactant 4

HCID 702EthanolHCID 8079CyclohexeneHCID 61373Oxalic acid dihydrateHCID 58046370(S)-1-(4-benzylpiperazin-1-yl)-2-hydroxypropan-1-one

Product 1

HCID 73603469(S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one oxalate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Ethanol (350 kg), Palladium (10% on activated carbon) (8.40 kg, 7.89 mol) and (S)-1-(4-benzylpiperazin-1-yl)-2-hydroxypropan-1-one 5 (70.0 kg, 282 mol) were charged to a reactor and the mixture was purged with nitrogen and heated to reflux. Cyclohexene (70.0 kg, 852 mol) was slowly added. The reaction mixture was heated to reflux and stirred for 24 h. After cooling to ambient temperature, the mixture was filtered through a pad of CELITE® and the cake was washed with ethanol (20 kg). The filtrate was cooled to 10-15° C. and a solution of oxalic acid dihydrate (36.0 kg, 286 mol) in tetrahydrofuran (156 kg) was slowly added at a rate to maintain the reaction temperature at 10-20° C. After aging for 2 h, the solid was collected by filtration, washed with ethanol (100 kg) and dried under reduced pressure at 50-55° C. to afford (S)-2-hydroxy-1-(piperazin-1-yl)propan-1-one oxalate salt V (58.2 kg, 83%). 1H NMR (300 MHz, D2O) δ 4.73-4.51 (m, 1H), 3.93-3.59 (m, 4H), 3.26 (dd, J=8.8, 4.0 Hz, 4H), 1.27 (d, J=6.7 Hz, 3H).

Workup

  1. customthe mixture was purged with nitrogen
  2. temperatureheated to reflux
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux
  5. filtrationthe mixture was filtered through a pad of CELITE®
  6. washthe cake was washed with ethanol (20 kg)
  7. temperatureThe filtrate was cooled to 10-15° C.
  8. temperatureto maintain the reaction temperature at 10-20° C
  9. waitAfter aging for 2 h
  10. filtrationthe solid was collected by filtration
  11. washwashed with ethanol (100 kg)
  12. customdried under reduced pressure at 50-55° C.

Sources & evidence

ORD record
ord-523f24f22b6840bfb40c109c6cdf7ac9
Source dataset
uspto-grants-2014_11
Patent number
US08895729B2

Reaction notes

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