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 339244Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 339244
[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]

Komponenten

6

Edukt 4

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

Produkt 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-dicarboxylateAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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)+.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-8e4d901c20154ca5877e75cb2596283a
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889712B2

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