Ethyl propiolate → HCID 18549368, compound

HRID 540749Notes

Reaction equation

HRID 540749 reaction equation
C([Li])CCC.[C:6]([O:10][CH2:11][CH3:12])(=[O:9])[C:7]#[CH:8].I[C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[C:17]#[N:18]>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:17]([C:16]1[CH:15]=[C:14]([C:8]#[C:7][C:6]([O:10][CH2:11][CH3:12])=[O:9])[CH:21]=[CH:20][CH:19]=1)#[N:18]

Participants

7

Reactant 3

HCID 12182Ethyl propiolateHCID 1443413-IodobenzonitrileHCID 178418339Butyllithium

Product 1

HCID 18549368HCID 18549368, compoundYield 51.1%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyllithium (2.50 Min hexanes, 16.8 mL, 41.9 mmol 1.20 equiv) was added dropwise to a solution of ethyl propiolate (4.11 g, 41.9 mmol, 1.20 equiv) in tetrahydrofuran (350 mL) at −78° C. After stirring for 15 minutes at −78° C., a solution of zinc chloride (1.0 M in diethyl ether, 84 mL, 84 mmol, 2.4 equiv) was added and the cooling bath was removed. After stirring for 2 hours, 3-iodobenzonitrile 8.00 g (34.9 mmol, 1 equiv) and Pd(Ph3P)4 (2.0 g, 1.7 mmol, 0.05 equiv) were added and the reaction mixture was heated to 50° C. After stirring for 90 minutes, the reaction mixture was cooled to 22° C. and filtered. The filtrate was concentrated to ˜½ volume, then was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated. The residue was purified by flash-column chromatography on silica gel (hexanes, grading to 50% ethyl acetate-hexanes) to afford ethyl 3-(3-cyanophenyl)prop-2-ynoate (3.55 g, 51%) as a light-orange solid. Calcd (M+1)+: 200.1. Found: 200.1.

Workup

  1. customthe cooling bath was removed
  2. stirringAfter stirring for 2 hours
  3. temperaturethe reaction mixture was heated to 50° C
  4. stirringAfter stirring for 90 minutes
  5. temperaturethe reaction mixture was cooled to 22° C.
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customwas partitioned between ethyl acetate and water
  9. washThe organic layer was washed with saturated aqueous sodium chloride solution
  10. dry with materialdried over sodium sulfate
  11. filtrationThe dried solution was filtered
  12. concentrationthe filtrate was concentrated
  13. customThe residue was purified by flash-column chromatography on silica gel (hexanes, grading to 50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-c75dd1e0951a4d9d91e7de94c62b8ae5
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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