Methanol → Methyl (δS)-δ-[[(S)-(1,1-dimethylethyl)sulfinyl]amino]-3,5-difluoro-α,α-dimethylbenzenepentanoate

HRID 1615818Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1615818
[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.[CH3:20][C:21]([S@@:24]([NH2:26])=[O:25])([CH3:23])[CH3:22].[BH4-].[Na+].CO>C1COCC1.[Cl-].[Na+].O.[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[C:21]([S@@:24]([NH:26][C@H: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:25])([CH3:23])([CH3:22])[CH3:20]

Komponenten

8

Edukt 4

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 57974028Methyl 3,5-difluoro-α,α-dimethyl-δ-oxobenzenepentanoate

Produkt 1

HCID 66864959Methyl (δS)-δ-[[(S)-(1,1-dimethylethyl)sulfinyl]amino]-3,5-difluoro-α,α-dimethylbenzenepentanoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 76524Titanium tetraethoxideKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of methyl 5-(3,5-difluorophenyl)-2,2-dimethyl-5-oxopentanoate from Step D (500. mg, 1.85 mmol) and (S)-2-methylpropane-2-sulfinamide (336 mg, 2.78 mmol) in THF (6.5 mL), was added titanium tetraethoxide (616 mg, 2.52 mmol). The reaction vessel was quickly sealed and heated at 60° C. for 3 h. After cooling to ambient temperature a septum and nitrogen inlet were attached prior to cooling to 0° C. Sodium borohydride (191 mg, 5.05 mmol) was then added, and a complete reaction was observed after 15 min. MeOH was slowly added until gas evolution stopped. The reaction mixture was diluted with saturated brine (6.5 mL) while experiencing rapid stirring. The resultant slurry was filtered through celite, washing with EtOAc as needed. The filtrate was 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 EtOAc:Hexanes—10:90 to 70:30, to give the title compound containing about 12% of the corresponding ethyl ester. MS: m/z=376 (M+1).

Aufarbeitung

  1. customThe reaction vessel was quickly sealed
  2. temperatureAfter cooling to ambient temperature a septum and nitrogen inlet
  3. temperatureto cooling to 0° C
  4. customa complete reaction
  5. filtrationThe resultant slurry was filtered through celite
  6. washwashing with EtOAc
  7. washThe filtrate was washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give an oil
  12. customThis oil was purified by silica gel chromatography
  13. washeluting with a gradient of EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-6387eba26d0346048d936c985f9de184
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765759B2

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