Iodine → (S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate

HRID 1009119

Reaktionsgleichung

Reaktionsgleichung von HRID 1009119
II.[C:3]([O:7][C:8]([C@H:10]([CH2:15]I)[C:11]([O:13][CH3:14])=[O:12])=[O:9])([CH3:6])([CH3:5])[CH3:4].I[C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1.C1(P(C2C=CC=CC=2C2C(OC)=CC=CC=2OC)C2CCCCC2)CCCCC1>CN(C=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:3]([O:7][C:8]([C@@H:10]([CH2:15][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)[C:11]([O:13][CH3:14])=[O:12])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Komponenten

8

Edukt 4

HCID 807IodineHCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 86614124(R)-methyl2-(tert-butoxycarbonyl)-3-iodopropanoate

Produkt 1

HCID 67270692(S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Iodine (0.0140 g, 0.0553 mmol) was added to zinc (0.542 g, 8.29 mmol) and the solid mixture was heated under vacuum for 10 minutes. The flask was flushed with nitrogen three times and allowed to cool. DMF (0.5 mL, degassed with nitrogen) was added and the suspension was cooled to 0° C. and stirred while (R)-methyl 2-(tert-butoxycarbonyl)-3-iodopropanoate (1.82 g, 5.53 mmol) in DMF (2.8 mL) was added dropwise. The mixture was stirred for 30 minutes at 0° C. and then allowed to come to RT for 30 minutes. 1-Iodo-4-(trifluoromethyl)benzene (1.50 g, 5.53 mmol), tris(dibenzylideneacetone)dipalladium (0.101 g, 0.111 mmol), and dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-Phos) (0.182 g, 0.442 mmol) were added. The flask was purged with nitrogen and heated at 40° C. After 3 hours the reaction was allowed to cool and partitioned between EtOAc and an aqueous solution of 9:1 saturated ammonium chloride/ammonium hydroxide. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water, brine, and dried over sodium sulfate. Concentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc) afforded (S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate.

Aufarbeitung

  1. temperaturethe solid mixture was heated under vacuum for 10 minutes
  2. customThe flask was flushed with nitrogen three times
  3. temperatureto cool
  4. additionDMF (0.5 mL, degassed with nitrogen) was added
  5. additionwas added dropwise
  6. waitto come to RT for 30 minutes
  7. customThe flask was purged with nitrogen
  8. temperatureheated at 40° C
  9. waitAfter 3 hours the reaction was allowed
  10. temperatureto cool
  11. custompartitioned between EtOAc
  12. extractionThe aqueous layer was extracted with EtOAc
  13. washthe combined organic layers were washed with water, brine
  14. dry with materialdried over sodium sulfate
  15. concentrationConcentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-ab28d83de962415d82b7e43b178ac308
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07973047B2

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