1-Benzyl-4-piperidone → (+/-)-2-(3,4-Difluorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole
Reaction equation
Br[C:2]1[C:3]([C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=2)[N:5]([Si](C(C)C)(C(C)C)C(C)C)[CH:6]=1.Br[C:32]1[C:33](C2C=CN=CC=2)=[C:34]([C:47]2[CH:52]=[CH:51][C:50](F)=CC=2)[N:35]([Si](C(C)C)(C(C)C)C(C)C)[CH:36]=1.C1C2N(CCC(=O)C2)CC1.C(N1CCC(=O)CC1)C1C=CC=CC=1>>[F:24][C:19]1[CH:18]=[C:17]([C:4]2[NH:5][CH:6]=[C:2]([C:52]3[CH2:47][CH:34]4[N:35]([CH2:36][CH2:32][CH2:33]4)[CH2:50][CH:51]=3)[C:3]=2[C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)[CH:22]=[CH:21][C:20]=1[F:23]Participants
Reactant 4
Product 1
Procedure
In a similar manner to the procedures described in Examples 9(i) and 9(iii) above, coupling, dehydration and desilylation reactions were carried out using 4-bromo-2-(3,4-difluorophenyl)-3-(pyridin-4-yl)-1-triisopropylsilyl-1H-pyrrole (prepared as described in Preparative Example 5 below), instead of 4-bromo-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1-triisopropylsilyl-1H-pyrrole, and (±)-1,2,3,5,6,7,8,8a-octahydroindolizine-7-one, instead of 1-benzylpiperidine-4-one, as starting materials to afford a mixture of the title compound and the (1,2,3,5,6,8a-hexahydroindolizin-7-yl) isomer thereof (which is the compound of Example 92 below). The mixture was separated by chromatography on a silica gel column using a 100:10:1 by volume mixture of ethyl acetate, methanol and isopropylamine as the eluant to give the title compound (yield 29%, Rf value=0.66) as a pale pink powder.
Workup
- customto afford
Sources & evidence
- ORD record
- ord-e166af251ba5464fac11eeac50abbca7
- Source dataset
- uspto-grants-2006_10
- Patent number
- US07122666B2
Reaction notes
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