Ethyl Acetate → HCID 178481515, compound

Participants

Reaction Steps

To a mixture of (S)-methyl 3-((R)-1,1-dimethylethylsulfinamido)-3-(tetrahydro-2H-pyran-4-yl)butanoate 5 (6.5 g, 21 mmol), DCM (70 mL), and MeOH (35 mL) was added hydrogen chloride solution (4.0 M in 1,4-dioxane, 79.8 mL). The resulting mixture was stirred at RT for 2 h. At that time, the reaction was concentrated and then diluted with toluene (100 mL) and re-concentrated. This material was dissolved in DMF (100 mL) and N-tert-butylcarbamoyl-N′-methylthiourea (5.06 g, 26.6 mmol), N,N-diisopropylethylamine (16.7 mL, 95.8 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.12 g, 31.9 mmol) were added. The mixture was immersed in a 45° C. oil bath and allowed to stir overnight. After 16 h, the reaction was diluted with water (200 mL), 3N HCl (50 mL) and EtOAc and stirred vigorously for 10 min. The phases were separated and the aqueous layer was extracted 2× with EtOAc. The organic portions were combined, washed with sat. aq. NaHCO3 and brine, dried over MgSO4, filtered and concentrated. This crude sample was subjected to column chromatography (ISCO, 330 g silica, 100 ml/min, 0% to 100% EtOAc/hexanes) to give (S)-tert-butyl 1,4-dimethyl-6-oxo-4-(tetrahydro-2H-pyran-4-yl)tetrahydropyrimidin-2(1H)-ylidenecarbamate 6 (5.9 g, 85%). 1H NMR (400 MHz, CDCl3) for 6: δ=9.98 (s, 1 H), 4.03 (m, 2 H), 3.34 (m, 2 H), 3.27 (s, 3 H), 2.62 (ABq, JAB=16.4 Hz, ΔνAB=66.8 Hz, 2 H), 1.66 (m, 1 H), 1.57 (m, 2 H), 1.49 (s, 9 H), 1.43 (m, 3 H), 1.25 (s, 3 H). LCMS for 6 (conditions D): tR=1.86 min, m/e=326.3 (M+H), 270.2 (M−t−Bu+H, base).

Provenance & Evidence