Phenylacetylene → HCID 18972712, compound

HRID 1377466Notes

Reaction equation

HRID 1377466 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)#[CH:2].C([Mg]Br)C.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[C:21](=[O:26])[C:22]([Cl:25])([F:24])[F:23]>CCOCC.C1COCC1>[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[C:21]([OH:26])([C:2]#[C:1][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:22]([Cl:25])([F:23])[F:24]

Participants

6

Reactant 3

HCID 10821PhenylacetyleneHCID 18972705HCID 18972705, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 18972712HCID 18972712, compoundYield 71.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a 100 mL, 3 necked, oven dried round bottomed flask, with a stirring bar, argon inlet, reflux condenser, and a septum was added ethynyl benzene (2.13 g, 20.83 mmol), dry THF (50 mL) and ethyl magnesium bromide (6.94 mL of a 3.0M solution in ether). This mixture was aged 2h at ambient temperature then a solution of 1-(2-amino-5-chlorophenyl)-2-chloro-2,2-difluoroethanone (1.00 g, 4.17 mmol) in THF (6 mL) was added with a syringe. The resulting orange-red solution was stirred at ambient temperature for 21.5 h. The reaction was quenched by addition of 1N HCl (50 mL) then diluted with EtOAc. The solution was then made basic with concentrated NH4OH and the layers were separated. The organic phase was washed with water and brine. Drying (MgSO4), filtration, removal of the solvent in vacuo, and chromatography on silica gel using 20% EtOAc in hexane as eluant gave 1.02 g of (±) 2-(2-amino-5-chlorophenyl)-4-phenyl-1-chloro-1,1-difluoro-3-butyn-2-ol as an off white solid. 1H NMR (CDCl3): δ4.42 (br s, 2H), 5.10 (br s, 1H), 6.65 (d, 1H, J=8.5 Hz), 7.15 (dd, 1H, J=2.4, 8.5 Hz), 7.38 (m, 3H), 7.55 (m, 2H), 7.70 (d, J=2.4 Hz).

Workup

  1. customTo a 100 mL, 3 necked, oven dried round bottomed flask
  2. temperaturewith a stirring bar, argon inlet, reflux condenser
  3. customat ambient temperature
  4. customThe reaction was quenched by addition of 1N HCl (50 mL)
  5. additionthen diluted with EtOAc
  6. customthe layers were separated
  7. washThe organic phase was washed with water and brine
  8. customDrying
  9. filtration(MgSO4), filtration, removal of the solvent in vacuo, and chromatography on silica gel using 20% EtOAc in hexane as eluant

Sources & evidence

ORD record
ord-6b8d146485194e128e28e301bdebd4b4
Source dataset
uspto-grants-1997_09
Patent number
US05665720

Reaction notes

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