Water → 4-Chloro-alpha-cyclopropyl-alpha-methylbenzenemethanol

HRID 561462

Reaction equation

HRID 561462 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1)=[O:3].[CH:11]1([Mg]Br)[CH2:13][CH2:12]1.O.C(#N)C>C(OCC)C.O1CCCC1>[CH:11]1([C:2]([C:4]2[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=2)([OH:3])[CH3:1])[CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 962WaterHCID 6342AcetonitrileHCID 7467P-ChloroacetophenoneHCID 178418630HCID 178418630, compound

Product 1

HCID 234634-Chloro-alpha-cyclopropyl-alpha-methylbenzenemethanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1.50 g (9.70 mmol) of 4-chloroacetophenone were dissolved in 8 ml of diethyl ether at 0° C., and 38.8 ml (19.41 mmol) of a 0.5N solution of cyclopropylmagnesium bromide in tetrahydrofuran were slowly added dropwise. Stirring at 0° C. for 1 h was followed by warming to RT, addition of water and acetonitrile to the reaction solution, and filtration of the mixture through kieselguhr. The organic solvents were removed in a rotary evaporator, and the aqueous phase was extracted twice with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution, and the solvents were removed in vacuo. The crude product was purified twice by preparative HPLC (mobile phase: acetonitrile/water gradient). The acetonitrile was removed from the combined product phases in a rotary evaporator, and the aqueous phase was extracted twice with diethyl ether. The combined organic phases were again washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the solvents were removed in vacuo. 1.37 g (72% of theory) of the title compound were obtained.

Workup

  1. temperatureby warming to RT
  2. filtrationto the reaction solution, and filtration of the mixture through kieselguhr
  3. customThe organic solvents were removed in a rotary evaporator
  4. extractionthe aqueous phase was extracted twice with diethyl ether
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  6. customthe solvents were removed in vacuo
  7. customThe crude product was purified twice by preparative HPLC (mobile phase: acetonitrile/water gradient)
  8. customThe acetonitrile was removed from the combined product phases in a rotary evaporator
  9. extractionthe aqueous phase was extracted twice with diethyl ether
  10. washThe combined organic phases were again washed with saturated aqueous sodium chloride solution
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-c7474b85547b455f9308765e46716d1f
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Linked notes

Loading…