Methanol → N2-(t-butoxycarbonyl)-N,N2,O-trimethyl-3-oxoserinamide

HRID 1519654Notes

Reaction equation

HRID 1519654 reaction equation
[CH3:1][NH2:2].CO.CO.[C:7]([O:11][C:12]([N:14]([CH:16]([C:22]([O:24]CC)=O)[C:17]([O:19][CH2:20]C)=[O:18])[CH3:15])=[O:13])([CH3:10])([CH3:9])[CH3:8].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OCC)(=O)C>[C:7]([O:11][C:12]([N:14]([CH3:15])[C@H:16]([C:22]([NH:2][CH3:1])=[O:24])[C:17](=[O:18])[O:19][CH3:20])=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

6

Reactant 4

HCID 887MethanolHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 57454252Monomethylamine methanol2×HCID 86679244Diethyl [(t-butoxycarbonyl)(methyl)amino]propanedioate2×

Product 1

HCID 86679245N2-(t-butoxycarbonyl)-N,N2,O-trimethyl-3-oxoserinamideYield 34%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 40% methylamine-methanol solution (67 mL) was added to a methanol (2.1 L) solution of diethyl [(t-butoxycarbonyl)(methyl)amino]propanedioate (Intermediate 3-1, 0.21 kg), and the mixture was stirred for 19 hours at room temperature. Further, a 40% methylamine-methanol solution (23 mL) was added, and the mixture was stirred for 4 days at the same temperature. Then, ethyl acetate (0.30 L) was added, and citric acid monohydrate (81 g) was slowly added under ice cooling, followed by stirring the mixture for 30 minutes under ice cooling. The precipitated solid was filtered, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with hexane/ethyl acetate=75/25→15/85) to obtain N2-(t-butoxycarbonyl)-N,N2,O-trimethyl-3-oxoserinamide (Intermediate 4-2, yellow oil) (63 g, 34%).

Workup

  1. stirringthe mixture was stirred for 4 days at the same temperature
  2. stirringby stirring the mixture for 30 minutes under ice cooling
  3. filtrationThe precipitated solid was filtered
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with hexane/ethyl acetate=75/25→15/85)

Sources & evidence

ORD record
ord-c2cc7ed1c3a446d7bd1598c997920759
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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