Dimethyl ethylidenemalonate → 1-Benzyl-2-(1-t-butoxycarbonylamino-2-methyl-propyl)-4-methyl-6-oxo-1,4,5,6-tetrahydro-pyrimidine-5-carboxylic acid methyl ester

HRID 1455148Notes

Reaction equation

HRID 1455148 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C@@H:8]([C:12](=[NH:21])[NH:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:9]([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].[CH:23](=[C:25]([C:30](OC)=[O:31])[C:26]([O:28][CH3:29])=[O:27])[CH3:24]>CO>[CH3:29][O:28][C:26]([CH:25]1[C:30](=[O:31])[N:13]([CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:12]([CH:8]([NH:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:22])[CH:9]([CH3:11])[CH3:10])=[N:21][CH:23]1[CH3:24])=[O:27]

Participants

4

Reactant 2

HCID 581096Dimethyl ethylidenemalonateHCID 178448380HCID 178448380, compound

Product 1

HCID 575311891-Benzyl-2-(1-t-butoxycarbonylamino-2-methyl-propyl)-4-methyl-6-oxo-1,4,5,6-tetrahydro-pyrimidine-5-carboxylic acid methyl esterYield 64.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
110 °C

Procedure

To a solution of [(R)-1-(N-Benzyl-carbamimidoyl)-2-methyl-propyl]-carbamic acid t-butyl ester (7.08 g, 23 mMol) in MeOH (15 mL) was added Dimethyl ethylidenemalonate (3.64 g, 23 mMol). The reaction was slowly heated to 110° C. allowing the MeOH to distill off. The reaction was stirred for 5 h at 110° C. then allowed to cool to RT. Purification by flash chromatography (25% EtOAc, hexane) gave the title compound (6.37 g, 64%) as an oil: ˜(3:1) mixture of diastereomers by LCMS; MS (ES) m/e 432.2 and 432.4 (M+H)+.

Workup

  1. distillationto distill off
  2. temperatureto cool to RT
  3. customPurification by flash chromatography (25% EtOAc, hexane)

Sources & evidence

ORD record
ord-8427a563354d4a6fa33f4fcb644b0172
Source dataset
uspto-grants-2009_01
Patent number
US07482343B2

Reaction notes

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