Hydrochloric Acid → (4-Chloro-2,6-difluorophenyl)(cyclopropyl)methanol

HRID 561480Notes

Reaction equation

HRID 561480 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([F:10])[C:5]([CH:6]=[O:7])=[C:4]([F:11])[CH:3]=1.[CH:12]1([Mg]Br)[CH2:14][CH2:13]1.Cl.C(OCC)(=O)C>C(OCC)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([F:11])[C:5]([CH:6]([CH:12]2[CH2:14][CH2:13]2)[OH:7])=[C:8]([F:10])[CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 27735124-Chloro-2,6-difluorobenzaldehydeHCID 178418630HCID 178418630, compound

Product 1

HCID 58392245(4-Chloro-2,6-difluorophenyl)(cyclopropyl)methanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

2.00 g (11.33 mmol) of 4-chloro-2,6-difluorobenzaldehyde were dissolved in 15 ml of diethyl ether at 0° C., and 34.0 ml (16.99 mmol) of a 0.5N solution of cyclopropylmagnesium bromide in tetrahydrofuran were slowly added dropwise. After stirring at RT for 2 h, the reaction solution was mixed with 1N hydrochloric acid and ethyl acetate, and the phases were separated. The aqueous phase was extracted three times 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 by preparative HPLC (mobile phase: acetonitrile/water gradient). 1.20 g (48% of theory) of the title compound were obtained.

Workup

  1. customthe phases were separated
  2. extractionThe aqueous phase was extracted three times with diethyl ether
  3. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  4. customthe solvents were removed in vacuo
  5. customThe crude product was purified by preparative HPLC (mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-767555e71d2a4c4989899cbe0c7f47ed
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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