Acetone → methyl 2-[(3S,4R)-3-(1-hydroxy-1-methylethyl)-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoate

Temperatur

-70 °C

1.55M Butyl lithium-hexane solution (2.82 ml) was added to a solution of N-isopropylcyclohexylamine (0.72 ml) in tetrahydrofuran (6 ml) at -70° C., and the mixture was stirred for 20 minutes at -70° C. This mixture was added to a solution of methyl 3-methyl-2-[(4R)-2-oxo-4-allylazetidin-1-yl]but-2-enoate (247 mg) in tetrahydrofuran (6 ml) at -70° C. and the mixture was stirred for 1 hour at -70° C., and for 30 minutes at -30° C. Acetone (0.12 ml) was added to the reaction mixture at -70° C., and the mixture was stirred for 1 hour at -70° C. and for 30 minutes at -30° C.-15° C. 3N Hydrochloric acid was added to the reaction mixture at -70° C. and the mixture was diluted with ethyl acetate (200 ml). The solution was washed with water, brine, aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated in vacuo. Triethylamine (0.15 ml) was added to a solution of the residue in dichloromethane (3 ml) at 0° C. and the mixture was stirred overnight at ambient temperature. The reaction mixture was diluted with ethyl acetate (20 ml) and the solution was washed with 0.1N hydrochloric acid (15 ml) brine, aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed on silica gel (10 g) eluting with a mixture of benzene and acetone (10:1-2:1) to give methyl 3-methyl-2-[(3S, 4R)-3-(1-hydroxy-1-methylethyl)-2-oxo-4-allylazetidin-1-yl]but-2-enoate (100 mg); IR (CH2Cl2): 1740, 1715 cm-1. NMR (CDCl3) δ: 1.31 (s, 3H), 1.38 (s, 3H), 1.96 (s, 3H), 2.18 (s, 3H), 2.2-2.5 (m, 3H), 2.90 (d, 1H, J=3 Hz), 3.76 (s, 3H), 3.81 (dt, 1H, J=3, 7 Hz), 4.9-5.2 (m, 2H), 5.5-6.0 (m, 1H) and methyl 3-methyl-2-[(3R,4R)-3-(1-hydroxy-1-methylethyl)-2-oxo-4-allylazetidin-1-yl]but-2-enoate (50 mg).

1. stirringthe mixture was stirred for 1 hour at -70° C.
2. waitfor 30 minutes at -30° C
3. stirringthe mixture was stirred for 1 hour at -70° C. and for 30 minutes at -30° C.-15° C
4. washThe solution was washed with water, brine, aqueous sodium bicarbonate and brine
5. dry with materialdried over magnesium sulfate
6. customevaporated in vacuo
7. additionTriethylamine (0.15 ml) was added to a solution of the residue in dichloromethane (3 ml) at 0° C.
8. stirringthe mixture was stirred overnight at ambient temperature
9. additionThe reaction mixture was diluted with ethyl acetate (20 ml)
10. washthe solution was washed with 0.1N hydrochloric acid (15 ml) brine, aqueous sodium bicarbonate and brine
11. dry with materialdried over magnesium sulfate
12. customevaporated in vacuo
13. customThe residue was chromatographed on silica gel (10 g)
14. washeluting with a mixture of benzene and acetone (10:1-2:1)

ORD-Eintrag

ord-80729ba030d74ffe811900031ebfebd4

Quelldatensatz

uspto-grants-1985_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04539152