3,4-Difluorobenzylamine → [3-(4-Chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amine

HRID 597880

Reaktionsgleichung

Reaktionsgleichung von HRID 597880
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([CH:6]=[CH:7][CH:8]=O)=[CH:4][CH:3]=1.[F:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[F:21])[CH2:16][NH2:17].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([CH:6]=[CH:7][CH2:8][NH:17][CH2:16][C:15]2[CH:18]=[CH:19][C:20]([F:21])=[C:13]([F:12])[CH:14]=2)=[CH:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 1235723,4-DifluorobenzylamineHCID 3794977p-ChlorocinnamaldehydeHCID 5049666Sodium triacetoxyborohydride

Produkt 1

HCID 67271292[3-(4-Chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 63651,1-DichloroethaneLösungsmittel

Versuchsvorschrift

The cis-diaryl compounds were prepared as shown above. To a solution of 4-chlorocinnamaldehyde (1.45 g, 8.70 mmol) in 100 mL of dichloroethane was added 3,4-difluorobenzylamine followed by sodium triacetoxyborohydride (3.7 g, 17.5 mmol, 2 eq.). The mixture was stirred overnight at room temperature, washed with aq. NaHCO3, brine, dried over MgSO4, filtered, concentrated and chromatographed with 40% ethyl acetate-hexanes to provide 0.84 g of [3-(4-chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amine. The [3-(4-chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amine was coupled with 5-(2,4-dichloro-phenyl)-penta-2,4-dienoyl chloride to provide 5-(2,4-dichloro-phenyl)-penta-2,4-dienoic acid [3-(4-chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amide. When 5-(2,4-dichloro-phenyl)-penta-2,4-dienoic acid [3-(4-chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amide was subjected to the Diels-Alder reaction conditions shown above, it gave 60 as the major product. Epimerization of the trans-lactam gave 61 and reduction of the double bond of 61 gave 62.

Aufarbeitung

  1. washwashed with aq. NaHCO3, brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customchromatographed with 40% ethyl acetate-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-0c27f043108049689a4450b37d9522c9
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07897601B2

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