反応式
[C:1]1([C:7](=[N+]=[N-])[C:8]([O:10][CH3:11])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)(OC(C)(C)C)=O.FC(F)(F)C(O)=O>CC(C(C)C)C.CCCCCCCCCCCCC1C=CC(S(N2[C@H](C(O)=O)CCC2)(=O)=O)=CC=1.CCCCCCCCCCCCC1C=CC(S(N2[C@H](C(O)=O)CCC2)(=O)=O)=CC=1.CCCCCCCCCCCCC1C=CC(S(N2[C@H](C(O)=O)CCC2)(=O)=O)=CC=1.CCCCCCCCCCCCC1C=CC(S(N2[C@H](C(O)=O)CCC2)(=O)=O)=CC=1.[Rh].[Rh]>[CH3:11][O:10][C:8]([C@@H:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C@@H:22]1[NH:21][CH2:26][CH2:25][CH2:24][CH2:23]1)=[O:9]参加物
反応物 3
生成物 1
試薬・触媒・溶媒 2
実験手順
As shown above in Scheme V and Table III, Rh2(S-DOSP)4 7 catalyzed decomposition of methyl phenyldiazoacetate 9a in the presence of N-BOC-piperidine (15, 4 equiv) in 2,3-dimethylbutane at room temperature followed by treatment with trifluoroacetic acid resulted in the formation of a mixture of threo and erythro methyphenidate, 16 and 17, in 49% yield. However, the threo isomer 16 was the minor diastereomer and was formed in only 34% ee. The combined yield of 16 and 17 was improved to 86% by using the N-BOC-peperidine as the limiting reactant. This result is different to what was observed with N-BOC-pyrrolidine, which gave bis C—H insertion when an excess of phenyldiazoacetate was used. A major improvement in enantioselectivity and diastereoselectivity was achieved by carrying out the reaction with the Rh2[bridged (S-TBSP)2]2 8 catalyst. The ratio of 16:17 (73% yield) was improved to 2.5:1 and (2R, 2′R)-threo isomer 16 was, formed in 86% ee and 52% isolated yield. As shown in Table III, Rh2[bridged (S-TBSP)2]2 8 results in opposite asymmetric induction to Rh2(S-DOSP)4 7, and, in the reaction of 9a and 15 catalyzed by 8, the biologically active enantiomer of threo-methylphenidate is formed.
出典と根拠
- ORDレコード
- ord-b1bac033e1b845c6a22ba5ed50f4e7b6
- 出典データセット
- uspto-grants-2004_07
- 特許番号
- US06762304B2
関連ノート
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