HCID 57974098, compound → Methyl 3,5-difluoro-α,α-dimethyl-δ-oxobenzenepentanoate

HRID 1866605Notes

Reaction equation

HRID 1866605 reaction equation
CON(C)[C:4](=[O:14])[CH2:5][CH2:6][C:7]([CH3:13])([CH3:12])[C:8]([O:10][CH3:11])=[O:9].[F:16][C:17]1[CH:18]=[C:19]([Mg]Br)[CH:20]=[C:21]([F:23])[CH:22]=1>C1COCC1>[F:16][C:17]1[CH:18]=[C:19]([C:4](=[O:14])[CH2:5][CH2:6][C:7]([CH3:12])([CH3:13])[C:8]([O:10][CH3:11])=[O:9])[CH:20]=[C:21]([F:23])[CH:22]=1

Participants

4

Reactant 2

HCID 57974098HCID 57974098, compoundHCID 178505930HCID 178505930, compound2×

Product 1

HCID 57974028Methyl 3,5-difluoro-α,α-dimethyl-δ-oxobenzenepentanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-[methoxy(methyl)amino]-2,2-dimethyl-5-oxopentanoate from Step C (4.68 g, 21.6 mmol) in THF (46.8 mL), cooled to 0° C., was added 3,5-difluorophenyl magnesium bromide (65 mL, 0.5 M in THF, 32.3 mmol) over 30 minutes. The reaction was allowed to stir at ambient temperature for 2 h, after which time no additional reaction progress was observed. Additional 3,5-difluorophenyl magnesium bromide (50 mL, 0.5 M in THF, 25.0 mmol) was added over 30 minutes. After 3 h at 0° C., the reaction was quenched by the rapid addition of a cold (0° C.) solution of EtOH (71 mL) and conc. HCl (5.0 mL). The reaction was then diluted with water (200 mL) and diethyl ether (400 mL). The organics were washed with water (200 mL×3) and brine (100 mL), then dried over sodium sulfate, filtered, and concentrated in vacuo to give a residue. This residue was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:hexanes—50:50 to 100:0, to give the title compound. MS: m/z=239 (M−31(MeO−)).

Workup

  1. waitAfter 3 h at 0° C.
  2. customthe reaction was quenched by the rapid addition of a cold (0° C.) solution of EtOH (71 mL) and conc. HCl (5.0 mL)
  3. additionThe reaction was then diluted with water (200 mL) and diethyl ether (400 mL)
  4. washThe organics were washed with water (200 mL×3) and brine (100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a residue
  9. customThis residue was purified by silica gel chromatography
  10. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-cdd2e5ce1bc143a4a0834fcff0846fa4
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

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