Triphenylphosphine → (2S,4S)-1-tert-Butyl 2-methyl 4-(((S)-2-(tert-butoxycarbonyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)pyrrolidine-1,2-dicarboxylate

HRID 339244ノート

反応式

HRID 339244 の反応式
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][C@@H:7]([C:19](=[O:31])[NH:20][C@H:21]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][CH2:23][CH2:22]3)[N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O[C@H:52]1[CH2:56][N:55]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C@H:54]([C:64]([O:66][CH3:67])=[O:65])[CH2:53]1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C(Cl)Cl>[C:15]([O:14][C:12]([N:8]1[C@H:7]([C:19](=[O:31])[NH:20][C@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24][CH2:23][CH2:22]2)[CH2:6][C:5]2[C:10](=[CH:11][C:2]([O:1][C@@H:52]3[CH2:56][N:55]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C@H:54]([C:64]([O:66][CH3:67])=[O:65])[CH2:53]3)=[CH:3][CH:4]=2)[CH2:9]1)=[O:13])([CH3:16])([CH3:17])[CH3:18]

参加物

6

反応物 4

HCID 11776Triphenylphosphine2 回HCID 730421,1'-(Azodicarbonyl)dipiperidine2 回HCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester2 回HCID 86705863(S)-tert-Butyl 7-hydroxy-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate2 回

生成物 1

HCID 86705879(2S,4S)-1-tert-Butyl 2-methyl 4-(((S)-2-(tert-butoxycarbonyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)pyrrolidine-1,2-dicarboxylate収率 86%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (S)-tert-butyl 7-hydroxy-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (Compound D of Example 1, 50 mg, 0.12 mmol) in CH2Cl2 (1.0 mL) was added PPh3 (37 mg, 0.14 mmol), (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (Aldrich, 35 mg, 0.14 mmol) and ADDP (37 mg, 0.14 mmol). The resulting reaction mixture was allowed to stir overnight at room temperature. Additional (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (35 mg, 0.14 mmol), PPh3 (37 mg, 0.14 mmol) and ADDP (37 mg, 0.14 mmol) were then added. The reaction mixture was allowed to stir at room temperature for 60 h, then concentrated in vacuo and purified using flash column chromatography (gradient from 0% to 60% EtOAc/hexanes) to give the title compound (66 mg, 86%) as a colorless oil. MS (ESI+) m/z 650.4 (M+H)+.

後処理

  1. customThe resulting reaction mixture
  2. stirringto stir at room temperature for 60 h
  3. concentrationconcentrated in vacuo
  4. custompurified

出典と根拠

ORDレコード
ord-8e4d901c20154ca5877e75cb2596283a
出典データセット
uspto-grants-2014_11
特許番号
US08889712B2

反応ノート

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