Methanol → 6-tert-Butyl 3-methyl (S)-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-3,6-dicarboxylate

HRID 481239Notes

Reaction equation

HRID 481239 reaction equation
[NH2:1][C:2]1[CH2:3][CH2:4][C@@H:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[N:6]=1.[CH3:14][OH:15]>>[O:15]=[C:14]1[N:6]2[C@H:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4][CH2:3][C:2]2=[N:1][CH:4]=[C:5]1[C:7]([O:9][CH3:10])=[O:8]

Participants

3

Reactant 2

HCID 887Methanol2×HCID 53795147tert-Butyl (S)-5-amino-3,4-dihydro-2H-pyrrole-2-carboxylate

Product 1

HCID 542728946-tert-Butyl 3-methyl (S)-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-a]pyrimidine-3,6-dicarboxylateYield 46%

Procedure

To a solution of dimethyl methoxymethylene malonate (8.68 g, 49.8 mmol) in 100 mL MeOH at −10° C., was added a solution of 1e (8.50 g, 46.1 mmol) in 100 mL MeOH over 1 h. The mixture was stirred at rt for 2 h, then was allowed to warm to rt overnight. The mixture was concentrated in vacuo and the resultant residue was purified by flash chromatography (50 to 100% EtOAc/hexanes) to afford 6.32 g (46%) of pyrimidinone 1f, as a colorless solid. 1H NMR (300 MHz, CDCl3) δ8.69 (s, 1H), 5.03 (dd, J=9.7, 2.8, 1H), 3.90 (s, 3H), 3.38-3.09 (m, 2H), 2.64-2.49 (m, 1H), 2.34-2.23 (m, 1H), 1.49 (s, 9H).

Workup

  1. temperatureto warm to rt overnight
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe resultant residue was purified by flash chromatography (50 to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6fa401e8592945feaa3edcbe2c62d525
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

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