[3-(4-Chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amine → 5-(2,4-Dichloro-phenyl)-penta-2,4-dienoic acid [3-(4-chloro-phenyl)-allyl]-(3,4-difluoro-benzyl)-amide
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][CH2:10][NH:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)=[CH:4][CH:3]=1.[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[CH:29]=[CH:30][CH:31]=[CH:32][C:33](Cl)=[O:34]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]=[CH:9][CH2:10][N:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[C:33](=[O:34])[CH:32]=[CH:31][CH:30]=[CH:29][C:23]2[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:22]=2[Cl:21])=[CH:6][CH:7]=1Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-9d21f23d67374474b8ad8600e008b587
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07897601B2
Reaction notes
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