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

HRID 1737852Notes

Reaction equation

[CH3:1][O-].[Na+].[C:4]([O:8][C:9]([C@H:11]1[N:15]=[C:14]([NH2:16])[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5].Cl.[C:18]1(=[O:29])O[CH:23](OC(C)C)[O:22][C:20](=[O:21])[CH2:19]1>CO>[CH3:23][O:22][C:20]([C:19]1[C:18](=[O:29])[N:15]2[C@H:11]([C:9]([O:8][C:4]([CH3:7])([CH3:5])[CH3:6])=[O:10])[CH2:12][CH2:13][C:14]2=[N:16][CH:1]=1)=[O:21]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of freshly prepared sodium methoxide (Na, 50% by weight in paraffin, 0.084 g, 1.84 mmol, 2.25 mL anh MeOH) was added slowly to a solution of (S)-2-amino-3,4-dihydro-5H-pyrrole-5-carboxylic acid t-butyl ester.HCl (0.41 g, 1.84 mmol) in 2.25 mL anh MeOH cooled to -10° C. After 1 h, the resulting white precipitate (NaCl) was filtered, and the solution of this free base was slowly added to a solution of dimethylmethoxymethylene malonate (0.32 g, 1.84 mmol) in 2.25 mL anh MeOH at -10° C. The reaction mixture was stirred at 0° C. overnight at which time it was concentrated under vacuum, and the residue was purified by column chromatography on silica gel (2% MeOH/CHCl3) to afford (S)-4-oxo-4,6,7,8-tetrahydropyrrolo[1,2-α]pyrimidine-3,6-dicarboxylic acid 6-t-butyl ester 3-methyl ester (0.22 g, 40%) as a yellow oil. 1H NMR (CDCl3) δ 1.49 (s, 9H), 2.31 (m, 1H), 2.57 (m, 1H), 3.09-3.33 (m, 2H), 3.90 (s, 3H), 5.03 (m, 1H), 8.69 (s, 1H). MS calcd C14H18N2O5 +295, found 295.

Workup

filtrationthe resulting white precipitate (NaCl) was filtered
concentrationwas concentrated under vacuum
customthe residue was purified by column chromatography on silica gel (2% MeOH/CHCl3)

Sources & evidence

ORD record: ord-a626e11fbbcd4486acc510b0b30b71b5
Source dataset: uspto-grants-1999_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05962487

Reaction notes

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