Tetrahydrofuran → Ethyl 2-{[(2R)-2-[(tert-butylsulfinyl)amino]-2-(3,5-difluorophenyl)ethyl]thio}-2-methylpropanoate

HRID 1866610Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1866610
[F:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][S: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+].[CH2:29]1COCC1>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[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][S:11][C:12]([CH3:18])([CH3:17])[C:13]([O:15][CH2:16][CH3:29])=[O:14])=[O:25])([CH3:23])([CH3:22])[CH3:20]

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 66973283Methyl 2-{[2-(3,5-difluorophenyl)-2-oxoethyl]thio}-2-methylpropanoate

Produkt 1

HCID 66973449Ethyl 2-{[(2R)-2-[(tert-butylsulfinyl)amino]-2-(3,5-difluorophenyl)ethyl]thio}-2-methylpropanoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 76524Titanium tetraethoxideKatalysator

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To methyl 2-{[2-(3,5-difluorophenyl)-2-oxoethyl]thio}-2-methylpropanoate from Step B (500. mg, 1.74 mmol) was added (R)-(+)-2-methyl-2-propanesulfinamide (254 mg, 2.09 mmol) under a constant stream of nitrogen. The reagents were dissolved in THF (17 mL), and to the above mixture was added titanium ethoxide (796 mg, 3.49 mmol). The reaction was sealed and stirred at 60° C. for 15 hours. The reaction was complete as determined by LCMS analysis and transesterification was observed. The reaction was cooled gradually to 0° C. under nitrogen. To the reaction mixture was added sodium borohydride (132 mg, 3.49 mmol). The reaction was complete after fifteen minutes as indicated by LCMS analysis. The reaction was quenched after an additional twenty minutes of stirring with methanol until gas evolution ceased. Saturated brine (30 mL) was added with heavy stirring and the resulting slurry was filtered through celite and washed with aliquots of ethyl acetate. The organic layer was then washed with brine and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to provide a residue that was purified by silica gel chromatography, eluting with a gradient of EtOAc:Hexanes—20:80 to 75:25, to give the title compound (containing 10% of the undesired diastereomer). MS: m/z=408 (M+1).

Aufarbeitung

  1. customThe reaction was sealed
  2. temperatureThe reaction was cooled gradually to 0° C. under nitrogen
  3. waitThe reaction was complete after fifteen minutes
  4. customThe reaction was quenched after an additional twenty minutes
  5. stirringof stirring with methanol until gas evolution
  6. additionSaturated brine (30 mL) was added
  7. stirringwith heavy stirring
  8. filtrationthe resulting slurry was filtered through celite
  9. washwashed with aliquots of ethyl acetate
  10. washThe organic layer was then washed with brine
  11. dry with materialdried over sodium sulfate
  12. filtrationThe solution was filtered
  13. concentrationconcentrated in vacuo
  14. customto provide a residue that
  15. customwas purified by silica gel chromatography
  16. washeluting with a gradient of EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-a5e78aed6adc479eb75a7895be9742ee
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07629338B2

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