Water → Methyl 3-cyclopropyl-3-(4-chlorophenyl)propenoate

HRID 1588874Notes

Reaction equation

HRID 1588874 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([CH:23]2[CH2:25][CH2:24]2)=O)=[CH:17][CH:16]=1.O>O1CCCC1.CN(C)C=O.C(OCC)C>[CH:23]1([C:21]([C:18]2[CH:17]=[CH:16][C:15]([Cl:14])=[CH:20][CH:19]=2)=[CH:7][C:5]([O:4][CH3:3])=[O:6])[CH2:24][CH2:25]1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydride3×HCID 80029Trimethyl phosphonoacetate2×HCID 811484-Chlorophenyl cyclopropyl ketone

Product 1

HCID 53818028Methyl 3-cyclopropyl-3-(4-chlorophenyl)propenoateYield 921.8%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

A 50% suspension of 5.7 grams (0.012 mole) of sodium hydride in mineral oil was washed with three portions of tetrahydrofuran, and to this was added 21.7 grams (0.012 mole) of trimethyl phosphonoacetate in 300 mL of tetrahydrofuran. To the resultant thick mixture was added 150 ml of dimethylformamide. This was followed by the addition of a solution of 19.6 grams (0.011 mole) of cyclopropyl 4-chlorophenyl ketone in 50 ml of dimethylformamide. Upon completion of addition, the reaction mixture was heated to 80° C. and it was stirred for five hours. Gas chromatography of the reaction mixture indicated the presence of unreacted ketone. The reaction mixture was cooled, and an additional 1.0 gram of 97% sodium hydride was added. Upon completion of addition, the reaction mixture was again warmed to 80° C. and stirred for about 18 hours. Gas chromatography analysis of the reaction mixture indicated that unreacted ketone was still present. An additional 0.8 gram of 97% sodium hydride and 4.0 grams of trimethyl phosphonoacetate were added, and the reaction mixture was heated at 80° C. for an additional six hours. After this time the reaction mixture was cooled and poured into 500 ml of water and 300 ml of diethyl ether. The diethyl ether layer was separated, and the aqueous layer was extracted with five portions of diethyl ether. The ether layer and the extracts were combined and were washed with four portions of water. The aqueous layer and the water washes were combined and extracted with two portions of diethyl ether. The two ether extracts were combined and were washed with four portions of water. All of the organic layers and diethyl ether washes were combined and dried with magnesium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure, yielding 24.0 grams of methyl 3-cyclopropyl-3-(4-chlorophenyl)propenoate.

Workup

  1. additionUpon completion of addition
  2. temperatureThe reaction mixture was cooled
  3. additionUpon completion of addition
  4. temperaturethe reaction mixture was again warmed to 80° C.
  5. stirringstirred for about 18 hours
  6. temperaturethe reaction mixture was heated at 80° C. for an additional six hours
  7. temperatureAfter this time the reaction mixture was cooled
  8. customThe diethyl ether layer was separated
  9. extractionthe aqueous layer was extracted with five portions of diethyl ether
  10. washwere washed with four portions of water
  11. extractionextracted with two portions of diethyl ether
  12. washwere washed with four portions of water
  13. dry with materialdried with magnesium sulfate
  14. filtrationThe mixture was filtered
  15. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-856685273ef3424d8c4b16c2a86a1f76
Source dataset
uspto-grants-1993_06
Patent number
US05223536

Reaction notes

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