反应详情

To a 0.18 M solution of tetrahydrooxazine 33 (0.200 g, 0.514 mmol) in 9:1 MeCN/EtOH (2.9 mL) with MP-BH3CN (2.52 mmol/g, 0.204 g, 0.514 mmol) was added dropwise HCl (4.0 M in 1,4-dioxane, 0.515 mL, 2.06 mmol) with stirring. Stirring was continued for 3 h at rt, and then the solution was concentrated and purified by HPFC (95:5:1 to 90:10:1 CH2Cl2:EtOH:NH4OH). The product fractions were concentrated, diluted with EtOAc, and washed once with sat. NaHCO3 (aq) to remove excess ammonia salts. The aqueous fraction was back-extracted once with EtOAc. The combined organic fractions were dried with Na2SO4 and concentrated to afford 0.143 g of N-methyl tubuvaline ethyl ester 35 (97%) as a foamy solid. [α]25D=+70.5 (c=0.8, CHCl3). IR (film): 1087, 1232, 1315, 1492, 1713, 2947, 3119 cm−1. 1H NMR (500 MHz, d4-MeOD): δ 0.89 (d, 3H, J=6.8 Hz), 0.90 (d, 3H, J=6.8 Hz), 1.39 (t, 3H, J=7.0 Hz), 1.88-2.04 (m, 3H), 2.38 (s, 3H), 2.43-2.48 (m, 1H), 4.38 (q, 2H, J=7.0 Hz), 5.14-5.18 (m, 1H), 8.32 (s, 1H). 13C NMR (125 MHz, d3-MeCN): δ 14.6, 17.3, 20.1, 28.8, 33.1, 33.9, 61.9, 63.5, 72.1, 128.6, 148.2, 162.4, 180.8. HRMS (FAB) calcd. for C13H23N2O3S (M+H): 287.1429. Found 287.1427.

1. stirringStirring
2. concentrationthe solution was concentrated
3. custompurified by HPFC (95:5:1 to 90:10:1 CH2Cl2:EtOH:NH4OH)
4. concentrationThe product fractions were concentrated
5. additiondiluted with EtOAc
6. washwashed once with sat. NaHCO3 (aq)
7. customto remove excess ammonia salts
8. extractionThe aqueous fraction was back-extracted once with EtOAc
9. dry with materialThe combined organic fractions were dried with Na2SO4
10. concentrationconcentrated