3',5'-Difluoroacetophenone → 2-(3,5-Difluorophenyl)propan-2-ol

HRID 879098

Reaction equation

HRID 879098 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9](=[O:11])[CH3:10])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:12][Mg]Br>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9]([OH:11])([CH3:12])[CH3:10])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 2

HCID 5185963',5'-DifluoroacetophenoneHCID 178418573HCID 178418573, compound

Product 1

HCID 577321592-(3,5-Difluorophenyl)propan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(3,5-difluorophenyl)ethanone (1.0 equiv) in THF (0.2 M) at 0° C. was added methylmagnesium bromide (1.0 M in THF, 1.15 equiv). After stirring for 4 hours the reaction was quenched by addition of NH4Cl(sat.), diluted with EtOAc, washed with NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield 2-(3,5-difluorophenyl)propan-2-ol. To a solution of 2-(3,5-difluorophenyl)propan-2-ol in CH2Cl2 (0.1 M) at 0° C. was added 2.6 lutidine (6 equiv.) and than triisopropylsilyl trifluoromethanesulfonate (3.0 equiv.). After stirring for 3 hours at 0° C. and six hours at rt the solution was partitioned between EtOAc and NaHCO3(sat.), separated, washed with NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography to yield (2-(3,5-difluorophenyl)propan-2-yloxy)triisopropylsilane. (400 MHz, <cdcl3>) δ ppm 1.05-1.08 (m, 21H) 1.57 (s, 6H) 6.63 (s, 1H) 7.00 (dd, J=9.39, 2.35 Hz, 2H).

Workup

  1. customwas quenched by addition of NH4Cl(sat.)
  2. additiondiluted with EtOAc
  3. washwashed with NaCl(sat.)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by ISCO SiO2 chromatography

Sources & evidence

ORD record
ord-6df3b56e9d2c410d823e729d431456a4
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Linked notes

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