Benzyl 5-{[(S)-tert-butylsulfinyl]imino}-2,2-dimethylpentanoate → (S)-6-(3-Fluoro-4-methylphenyl)-3,3-dimethylpiperidin-2-one

HRID 1866645Notes

Reaction equation

HRID 1866645 reaction equation
C([S@@]([N:7]=[CH:8][CH2:9][CH2:10][C:11]([CH3:23])([CH3:22])[C:12](OCC1C=CC=CC=1)=[O:13])=O)(C)(C)C.[F:24][C:25]1[CH:26]=[C:27]([Mg]Br)[CH:28]=[CH:29][C:30]=1[CH3:31]>C1(C)C=CC=CC=1.C1COCC1>[F:24][C:25]1[CH:26]=[C:27]([C@H:8]2[NH:7][C:12](=[O:13])[C:11]([CH3:23])([CH3:22])[CH2:10][CH2:9]2)[CH:28]=[CH:29][C:30]=1[CH3:31]

Participants

5

Reactant 2

HCID 66973494Benzyl 5-{[(S)-tert-butylsulfinyl]imino}-2,2-dimethylpentanoate2×HCID 178426143HCID 178426143, compound

Product 1

HCID 66973541(S)-6-(3-Fluoro-4-methylphenyl)-3,3-dimethylpiperidin-2-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of benzyl (SS)-5-[(tert-butylsulfinyl)imino]-2,2-dimethylpentanoate (1.00 g, 2.96 mmol, described in Intermediate 3) in toluene (28 mL) at −78° C. was added 3-fluoro-4-methylphenylmagnesium bromide (11.9 mL of a 0.5 M solution in THF, 5.93 mmol). The reaction mixture was warmed to ambient temperature for 2 h, and then heated at reflux for 2 h. The solvent was removed in vacuo and the crude solid dissolved in DMSO (5 mL). The crude product was purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. Lyophilization provided the title compound. MS: m/z=236 (M+1).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 h
  3. customThe solvent was removed in vacuo
  4. dissolutionthe crude solid dissolved in DMSO (5 mL)
  5. customThe crude product was purified by HPLC
  6. washeluting with a gradient of H2O

Sources & evidence

ORD record
ord-b10c57efa5c74cf3ba1804670b88944c
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

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