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

HRID 1374859Notes

Reaction equation

HRID 1374859 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(OC)=O)[C:26](OC)=[O:27])[CH3:24]>CO>[CH2:14]([N:13]1[C:26](=[O:27])[CH2:25][CH:23]([CH3:24])[N:21]=[C:12]1[CH:8]([NH:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:22])[CH:9]([CH3:11])[CH3:10])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

4

Reactant 2

HCID 581096Dimethyl ethylidenemalonateHCID 178448380HCID 178448380, compound

Product 1

HCID 867603641-Benzyl-2-(1-t-butoxycarbonylamino-2-methyl-propyl)-4-methyl-6-oxo-1,4,5,6-tetrahydro-pyrimidineYield 74.2%

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-b5793c0e5f1743a4b6e5c5176f363627
Source dataset
uspto-grants-2007_01
Patent number
US07166595B2

Reaction notes

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