Hydrochloric Acid → methyl 3-methyl-2-[(3S,4R)-3-methyl-2-oxo-4-allylazetidin-1-yl]but-2-enoate

HRID 851392Notes

Reaction equation

HRID 851392 reaction equation
[CH:1](NC1CCCCC1)(C)C.[CH3:11][C:12]([CH3:26])=[C:13]([N:18]1[C@H:21]([CH2:22][CH:23]=[CH2:24])[CH2:20][C:19]1=[O:25])[C:14]([O:16][CH3:17])=[O:15].Cl>O1CCCC1.C(OCC)(=O)C>[CH3:11][C:12]([CH3:26])=[C:13]([N:18]1[C@H:21]([CH2:22][CH:23]=[CH2:24])[C@H:20]([CH3:1])[C:19]1=[O:25])[C:14]([O:16][CH3:17])=[O:15]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 62386CyclohexylisopropylamineHCID 54326273methyl 2-[(4R)-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoate

Product 1

HCID 56629339methyl 3-methyl-2-[(3S,4R)-3-methyl-2-oxo-4-allylazetidin-1-yl]but-2-enoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

1.55 M Butyl lithium-hexane solution (1.66 ml) was added to a solution of N-isopropylcyclohexylamine (0.29 ml) in tetrahydrofuran (3 ml) at -70° C., and the mixture was stirred for 20 minutes at -70° C. and allowed to warm up to 0° C. This mixture was added to a solution of methyl 3-methyl-2-[(4R)-2-oxo-4-allylazetidin-1-yl]but-2-enoate (100 mg) in tetrahydrofuran (3 ml) at -70° C., and the mixture was stirred for 1 hour at -70° C. and allowed to warm up to -30° C. during 30 minutes. 1 N Hydrochloric acid (3.6 ml) was added to the reaction mixture at -70° C., and the mixture was diluted with ethyl acetate (30 ml). The solution was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (5:1-2:1) to give methyl 3-methyl-2-[(3S,4R)-3-methyl-2-oxo-4-allylazetidin-1-yl]but-2-enoate (20 mg); IR (CH2Cl2): 1740, 1715 cm-1 ; NMR (CDCl3) δ: 1.23 (d, 3H, J=8 Hz), 1.95 (s, 3H), 2.19 (s, 3H), 1.36 (t, 2H, J=7 Hz), 3.36 (dq, 1H, J=6, 8 Hz), 3.75 (s, 3H), 4.04 (dt, 1H, J=6, 7 Hz), 4.9-5.2 (m, 2H), 5.4-5.9 (m, 2H); and methyl 3-methyl-2-[(3R,4R)-3-methyl-2-oxo-4-allylazetidin-1-yl]but-3-enoate (28 mg); IR (CH2Cl2): 1740 cm-1 ; NMR (CDCl3) δ: 1.27 and 1.29 (a pair of d, 3H, J=8 Hz), 1.83 (broad s, 3H), 2.1-2.9 (m, 2H), 2.85 (dq, 1H, J=2, 8 Hz), 3.2-3.4 (m, 1H), 3.74 and 3.76 (a pair of s, 3H), 4.8-5.2 (m, 5H), 5.5-6.0 (m, 1H); and a mixture of methyl 3-methyl-2-[(3R,4R)-3-methyl-2-oxo- 4-allylazetidin-1-yl]but-2-enoate and methyl 3-methyl-2-[(3S,4R)-3-methyl-2-oxo-4-allylazetidin-1-yl]but-3-enoate (36 mg): IR (CH2Cl2): 1740 cm-1.

Workup

  1. temperatureto warm up to 0° C
  2. stirringthe mixture was stirred for 1 hour at -70° C.
  3. temperatureto warm up to -30° C. during 30 minutes
  4. washThe solution was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated in vacuo
  7. customThe residue was chromatographed on silica gel eluting with a mixture of hexane and ethyl acetate (5:1-2:1)

Sources & evidence

ORD record
ord-a0ce475993454445af1524b6e61a5e57
Source dataset
uspto-grants-1983_05
Patent number
US04383945

Reaction notes

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