N-Methylbenzylamine → 3-[2(R)-Benzyl-3-(N-benzyl-N-methylaminocarbonyl)propionyl]-4(S)-isopropyl-2-oxazolidinone

HRID 1768858Notes

Reaction equation

HRID 1768858 reaction equation
[CH2:1]([C@H:8]([CH2:20][C:21]([O:23]CC1C=CC=CC=1)=O)[C:9]([N:11]1[C@@H:15]([CH:16]([CH3:18])[CH3:17])[CH2:14][O:13][C:12]1=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([NH:38][CH3:39])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C>C(O)C.[Pd]>[CH2:1]([C@H:8]([CH2:20][C:21]([N:38]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH3:39])=[O:23])[C:9]([N:11]1[C@@H:15]([CH:16]([CH3:18])[CH3:17])[CH2:14][O:13][C:12]1=[O:19])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 7669N-MethylbenzylamineHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 144294593-[2(R)-Benzyl-3-(benzyloxycarbonyl)propionyl]-4(S)-isopropyl-2-oxazolidinone

Product 1

HCID 150457533-[2(R)-Benzyl-3-(N-benzyl-N-methylaminocarbonyl)propionyl]-4(S)-isopropyl-2-oxazolidinoneYield 98%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of 1.03 g (2.52 mmole) of 3-[2(R)-benzyl-3-(benzyloxycarbonyl)propionyl]-4(S)-isopropyl-2-oxazolidinone (prepared as described in Preparation 13) in 20 ml of ethanol was stirred at room temperature for 4 hours under an atmosphere of hydrogen and in the presence of 100 mg of 10% w/w palladium-on-charcoal. The catalyst was then removed by filtration, and the filtrate was concentrated by distillation under reduced pressure. The residue was dissolved in 50 ml of anhydrous tetrahydrofuran, and 0.39 ml (3.02 mmole) of N-benzyl-N-methylamine, 0.46 ml of 95% diethyl cyanophosphonate and 0.42 ml of triethylamine were added, in that order, to the solution, whilst ice-cooling and under an atmosphere of nitrogen, after which the mixture was stirred for 6 hours. At the end of this time, the solvent was removed by distillation under reduced pressure, and the residue was purified by medium pressure column chromatography through silica gel using a 1:1 by volume mixture of ethyl acetate and hexane as the eluent), followed by recrystallization from diisopropyl ether, to afford 1.04 g (yield 98%) of the title compound as white crystals, melting at 60°-62° C.

Workup

  1. customThe catalyst was then removed by filtration
  2. concentrationthe filtrate was concentrated by distillation under reduced pressure
  3. dissolutionThe residue was dissolved in 50 ml of anhydrous tetrahydrofuran
  4. temperaturecooling and under an atmosphere of nitrogen
  5. customAt the end of this time, the solvent was removed by distillation under reduced pressure
  6. customthe residue was purified by medium pressure column chromatography through silica gel using a 1:1
  7. additionby volume mixture of ethyl acetate and hexane as the eluent),
  8. customfollowed by recrystallization from diisopropyl ether

Sources & evidence

ORD record
ord-bbcb2995c9f34d4cad349e1471ef5e43
Source dataset
uspto-grants-1995_01
Patent number
US05378689

Reaction notes

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