tert-Butylsulfinamide, (S)-(-)- → methyl (5E)-5-tert-butylsulfinylimino-5-(3,5-difluorophenyl)-2,2-dimethylpentanoate

HRID 1864920Notes

Reaction equation

HRID 1864920 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][CH2:11][C:12]([CH3:18])([CH3:17])[C:13]([O:15][CH3:16])=[O:14])[CH:5]=[C:6]([F:8])[CH:7]=1.CON(C)C(=O)CCC(C)(C)C(OC)=O.[CH3:35][C:36]([S@@:39]([NH2:41])=[O:40])([CH3:38])[CH3:37]>C1COCC1.[Cl-].[Na+].O.[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[C:36]([S:39](/[N:41]=[C:9](/[C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=1)\[CH2:10][CH2:11][C:12]([CH3:18])([CH3:17])[C:13]([O:15][CH3:16])=[O:14])=[O:40])([CH3:38])([CH3:37])[CH3:35]

Participants

7

Reactant 3

HCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 57974028Methyl 3,5-difluoro-α,α-dimethyl-δ-oxobenzenepentanoateHCID 57974098HCID 57974098, compound

Product 1

HCID 87221342methyl (5E)-5-tert-butylsulfinylimino-5-(3,5-difluorophenyl)-2,2-dimethylpentanoate

Reagents, catalysts & solvents 3

HCID 76524Titanium tetraethoxideCatalystHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of methyl 5-(3,5-difluorophenyl)-2,2-dimethyl-5-oxopentanoate from Intermediate 1, Step D (500 mg of 85% purity, 1.85 mmol) and (S)-2-methylpropane-2-sulfinamide (336 mg, 2.78 mmol) in THF (9.5 mL), was added titanium tetraethoxide (904 mg, 3.70 mmol). The reaction vessel was quickly sealed and placed into a 60° C. bath for 2 hours. After cooling to ambient temperature the reaction mixture was then diluted with saturated brine (9.5 mL) while experiencing rapid stirring. The resultant slurry was filtered through celite, washing with EtOAc, as needed. The combined organics were then washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of MeOH:CH2Cl2-0.5:99.5 to 3:97, to give the title compound. MS: m/z=374 (M+1).

Workup

  1. customThe reaction vessel was quickly sealed
  2. customplaced into a 60° C.
  3. customfor 2 hours
  4. filtrationThe resultant slurry was filtered through celite
  5. washwashing with EtOAc
  6. washThe combined organics were then washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give an oil
  11. customThis oil was purified by silica gel chromatography
  12. washeluting with a gradient of MeOH

Sources & evidence

ORD record
ord-ad92b9b2630640709e9a7fcf3bdff471
Source dataset
uspto-grants-2009_12
Patent number
US07625901B2

Reaction notes

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