Methyl thiocyanate → HCID 42642984, compound

Participants

Reaction Conditions

Reaction Steps

(S)-2-Mercapto-2,3-dimethylbutanoic acid (1.5 g, 0.01 mol) was dissolved in toluene (15 mL) under an atmosphere of nitrogen. Activated 3A sieves (1.5 g) and MeSCN (1.1 mL, 0.015 mol) were added and the resultant mixture was warmed to 110° C. The mixture was stirred for 2 h and cooled to 23° C. The mixture was treated with saturated aqueous NaHCO3 (20 mL), the phases were separated and the aqueous phase was extracted with EtOAc (3×15 mL). The combined organic phases were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. Chromatographic purification (10 g silica gel, 20-30% EtOAc/Hexanes) of the residual material yielded (S)-5-isopropyl-5-methyl-2-(methylthio)thiazol-4(5H)-one. This material was dissolved in MeOH (15 mL) and (S)-exo-aminonorbornane (1.35 g, 0.015 mol, 99.3% ee) was added under an atmosphere of nitrogen. The solution was stirred for 4 h and concentrated. Chromatographic purification (10 g silica gel, 10-40% EtOAc/Hexanes) of the residual material yielded 1.73 g (64%) of the title compound. 1H NMR (400 MHz, CDCl3, 90.15/9.85 mixture of diastereomers, signals for the major diastereomer) δ 3.33-3.40 (m, 1H), 2.36-2.45 (m, 2H), 2.21 (septaplet, 1H, J=8 Hz), 1.84-1.91 (m, 1H), 1.60-1.83 (m, 1H), 1.42-1.68 (m, 3H), 1.62 (s, 3H), 1.13-1.30 (m, 4H), 1.05 (d, 3H, J=8 Hz), 0.90 (d, 3H, J=8 Hz); 13C NMR (100 MHz, CDCl3, 90.15/9.85 mixture of diastereomers, signals for the major diastereomer) δ 191.1, 180.9, 70.9, 59.5, 43.0, 38.5, 35.9, 35.7, 35.6, 28.2, 26.6, 25.6, 19.0, 18.4; IR (neat): 3168, 2959, 2869, 1696, 1585, 1440, 1327, 1256, 1090, 1017, 829 cm−1; Exact Mass (C14H22N2OS+H): calculated=267.1526, measured=267.1525. Chiral LC: 90.15/9.85 dr.

Provenance & Evidence