tert-Butyl(2-fluorophenoxy)dimethylsilane → 1-(3-(tert-Butyldimethylsilyloxy)-2-fluorophenyl)-2-cyclopropylethanone

HRID 1662552

Reaction equation

HRID 1662552 reaction equation
[C:1]([Si:5]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].C([Li])(CC)C.[CH:21]1([CH2:24][C:25](N(OC)C)=[O:26])[CH2:23][CH2:22]1>C1COCC1>[Si:5]([O:8][C:9]1[C:10]([F:15])=[C:11]([C:25](=[O:26])[CH2:24][CH:21]2[CH2:23][CH2:22]2)[CH:12]=[CH:13][CH:14]=1)([C:1]([CH3:4])([CH3:2])[CH3:3])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 597214tert-Butyl(2-fluorophenoxy)dimethylsilaneHCID 224737662-cyclopropyl-N-methoxy-N-methylacetamideHCID 178418400CID 53628100

Product 1

HCID 577063151-(3-(tert-Butyldimethylsilyloxy)-2-fluorophenyl)-2-cyclopropylethanoneYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A 1 L round bottom flask was charged with 84.A (17.0 mL, 73.0 mmol) and THF (70 mL) and cooled to −78° C. under N2. To the cold solution was added sec-butyllithium (1.20 M/cyclohexane) (66.3 mL, 79.6 mmol) dropwise. The mixture was stirred for 30 minutes, and to it was added a solution of 84.B (9.31 mL, 66.3 mmol) in THF (70 mL) dropwise. The final mixture was stirred for 30 minutes at −78° C. The cooling bath was removed, and the mixture was stirred for 30 minutes at ambient temperature. The reaction was quenched with saturated aqueous NH4Cl (70 mL) and diluted with EtOAc (100 mL). The organic phase was washed with water (100 mL), 1 N HCl (100 mL) and brine (100 mL). The organic phase was then dried (MgSO4) and concentrated. The residue was purified by silica gel flash chromatography (2% EtOAc/hexane) to afford 84.C (14.9 g, 73% yield) as a yellow oil.

Workup

  1. customThe cooling bath was removed
  2. stirringthe mixture was stirred for 30 minutes at ambient temperature
  3. customThe reaction was quenched with saturated aqueous NH4Cl (70 mL)
  4. additiondiluted with EtOAc (100 mL)
  5. washThe organic phase was washed with water (100 mL), 1 N HCl (100 mL) and brine (100 mL)
  6. dry with materialThe organic phase was then dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel flash chromatography (2% EtOAc/hexane)

Sources & evidence

ORD record
ord-ab1e3df415bf45eb8f47d634656e800a
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Linked notes

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