Lithium Hexamethyldisilazide → HCID 178431774, compound

Temperature

-78 °C

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;

1. temperatureto warm up to rt
2. stirringstirred for 16 h
3. customThe resulting reaction mixture
4. extractionextracted with ethyl acetate (3×50 mL)
5. washwashed with brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customto give a crude product mixture
9. additionfollowed by addition of Mel (5.7 mL)
10. stirringThe reaction mixture was stirred at rt for 16 h
11. customfollowed by evaporation of solvent
12. customThe residue was partitioned between saturated NaHCO3 (10 mL) and EtOAc (15 mL)
13. customthe organic layer was separated
14. washwashed with brine
15. dry with materialdried (MgSO4)
16. concentrationThe solution was concentrated
17. customto give a yellow oil which
18. customwas purified by column chromatography

ORD record

ord-b0254ac18878451798b721ee516785ac

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07759353B2