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

HRID 851393Notes

Reaction equation

HRID 851393 reaction equation
[CH3:1][C:2]([CH3:16])=[C:3]([N:8]1[C@H:11]([CH2:12][CH:13]=[CH2:14])[CH2:10][C:9]1=[O:15])[C:4]([O:6][CH3:7])=[O:5].[CH3:17][C:18]([CH3:20])=[O:19].Cl>O1CCCC1.C(OCC)(=O)C>[CH3:1][C:2]([CH3:16])=[C:3]([N:8]1[C@H:11]([CH2:12][CH:13]=[CH2:14])[C@@H:10]([C:18]([OH:19])([CH3:20])[CH3:17])[C:9]1=[O:15])[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 3

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 54326273methyl 2-[(4R)-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoate

Product 1

HCID 22823199methyl 2-[(3S,4R)-3-(1-hydroxy-1-methylethyl)-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

1.55 M Butyl lithium-hexane solution (2.82 ml) was added to a solution of N-isopropylcyclohexylamino (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. 3 N 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 0.1 N 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). NMR (CDCl3) δ: 1.39 (s, 3H), 1.52 (s, 3H), 1.99 (s, 3H), 2.19 (s, 3H), 2.21 (broad s, 1H), 2.74 (t, 2H, J=7 Hz), 3.30 (d, 1H, J=6 Hz), 3.74 (s, 3H), 4.12 (dt, 1H, J=6, 7 Hz), 4.9-5.2 (m, 2H), 5.5-5.9 (m, 1H).

Workup

  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 0.1 N 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)

Sources & evidence

ORD record
ord-cd04639fab0642d48e1d536f8faa4cd6
Source dataset
uspto-grants-1983_05
Patent number
US04383945

Reaction notes

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