Lithium Hexamethyldisilazide → HCID 178431774, compound

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Reaction Conditions

Reaction Steps

The synthesis was adapted from the synthetic procedure by Pedregal et. al. Tetrahedron: Asymmetry 1994, 5, 921-926. Thus, to a solution of (S)-tert-butyl 4-(4-bromothiophen-2-yl)-1,4-dimethyl-6-oxo-tetrahydropyrimidin-2(1H)-ylidenecarbamate (C1, 1.0 g, 2.48 mmol) in anhydrous THF (7 mL) at −70° C. was added dropwise a solution of LiHMDS (1M, 5 mL, 2 eq, 4.96 mmol) in THF. After stirring at −78° C. for 40 min, N,N-dimethylmethylene iminium iodide (Eschenmoser's salt, 0.92 g, 4.96 mmol) was added. The reaction mixture was allowed to warm up to rt and stirred for 16 h. The resulting reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, washed with brine, dried (MgSO4), and concentrated in vacuo to give a crude product mixture containing C2 which was dissolved in methanol (8.0 mL), followed by addition of Mel (5.7 mL). The reaction mixture was stirred at rt for 16 h followed by evaporation of solvent. The residue was partitioned between saturated NaHCO3 (10 mL) and EtOAc (15 mL) and the organic layer was separated, washed with brine, dried (MgSO4). The solution was concentrated to give a yellow oil which was purified by column chromatography using 1:1 EtOAc/Hexane as eluent to give 0.88 g (85%) of (S)-tert-butyl 4-(4-bromothiophen-2-yl)-1,4-dimethyl-5-methylene-6-oxo-tetrahydropyrimidin-2(1H)-ylidenecarbamate C3 as a yellow oil. 1HNMR (CDCl3, 300 MHz): δ 7.14 (s, 1H), 6.8 (s, 1H), 6.49 (s, 1H), 5.73 (s, 1H), 3.29 (s, 3H), 1.52 (br s, 9H). MS (ESI): MH+=415.6; MH++1=416.6; M+−55=359.9;

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