4-Methylmorpholine → methyl (E)-2-(3-methylbenzylidene)-3-(cis-3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionate

HRID 1590176Notes

Reaction equation

HRID 1590176 reaction equation
[CH3:1][O:2][C:3](/[C:5](=[CH:10]/[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[CH:12]=1)/[CH2:6][C:7]([OH:9])=O)=[O:4].CN1CCOCC1.ClC(OCC(C)C)=O.[CH2:33]1[C@@H:41]2[C@@H:36]([CH2:37][CH:38]=[CH:39][CH2:40]2)[CH2:35][NH:34]1>O1CCCC1>[CH3:17][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=1)/[CH:10]=[C:5](\[CH2:6][C:7]([N:34]1[CH2:35][C@H:36]2[C@H:41]([CH2:40][CH:39]=[CH:38][CH2:37]2)[CH2:33]1)=[O:9])/[C:3]([O:2][CH3:1])=[O:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 16765331cis-2,3,3a,4,7,7a-Hexahydro-1h-isoindoleHCID 19769729(E)-3-Methoxycarbonyl-4-(3-methylphenyl)-3-butenoic acid

Product 1

HCID 86746700methyl (E)-2-(3-methylbenzylidene)-3-(cis-3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionateYield 29.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of (E)-3-methoxycarbonyl-4-(3-methylphenyl)-3-butenoic acid (1.05 g) in anhydrous tetrahydrofuran (20 ml) were added N-methylmorpholine (0.74 ml) and isobutyl chloroformate (0.75 ml) with stirring at -20° C. and the mixture was stirred for 20 minutes. To the mixture was added a solution of cis-3a,4,7,7a-tetrahydroisoindoline (773 mg) in anhydrous tetrahydrofuran (2 ml) with stirring at -20° C. After 1 hour, the deposit was filtered off and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with 1N hydrochloric acid, saturated sodium bicarbonate solution, and brine and dried over MgSO4. After the solvent was evaporated under reduced pressure, the residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (4/1) to give 446 mg of methyl (E)-2-(3-methylbenzylidene)-3-(cis-3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionate as a colorless viscous oil.

Workup

  1. stirringthe mixture was stirred for 20 minutes
  2. stirringwith stirring at -20° C
  3. filtrationthe deposit was filtered off
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washwashed successively with 1N hydrochloric acid, saturated sodium bicarbonate solution, and brine
  7. dry with materialdried over MgSO4
  8. customAfter the solvent was evaporated under reduced pressure
  9. customthe residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (4/1)

Sources & evidence

ORD record
ord-c30158b164224f249d12c8910bf0f372
Source dataset
uspto-grants-1993_04
Patent number
US05202335

Reaction notes

Loading…