Diisopropylethylamine → (2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate

HRID 523191Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 523191
[C:1]([O:5][C:6]([NH:8][CH:9]([C@H:13]([CH2:21][CH3:22])[CH2:14][CH:15]([CH3:20])[CH2:16][CH2:17][CH:18]=[CH2:19])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:56][C@H:57]1[CH2:61][NH:60][C@H:59]([C:62]([O:64][CH3:65])=[O:63])[CH2:58]1>ClCCl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([CH2:21][CH3:22])[CH2:14][CH:15]([CH3:20])[CH2:16][CH2:17][CH:18]=[CH2:19])[C:10]([N:60]1[CH2:61][C@H:57]([OH:56])[CH2:58][C@H:59]1[C:62]([O:64][CH3:65])=[O:63])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 7015125(4R)-4-Hydroxy-L-proline methyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86683261(3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoic acid

Produkt 1

HCID 86683260(2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylateAusbeute 53,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of (3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoic acid (2.0 g, 6.4 mmole) in dichloromethane (20 mL) was added DIPEA (1.93 mL, 19.2 mmole) and HATU (2.42 g, 6.38 mmole) followed by (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate (1.15 g, 6.38 mmole) at room temperature. The reaction mixture was stirred at room temperature for 2 h. The reaction mass was diluted with DCM and washed with water. The organic layer was dried over anhydrous Na2SO4; filtered; then concentrated under reduced pressure to get crude compound as mixture of diastereomers. The material was subjected to SFC purification to afford (2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3-ethyl-5-methylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (1.5 g, 53%). MS: MS m/z 441.6 (M++1).

Aufarbeitung

  1. washwashed with water
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationthen concentrated under reduced pressure
  5. customto get crude compound
  6. additionas mixture of diastereomers
  7. customThe material was subjected to SFC purification

Quellen und Nachweise

ORD-Eintrag
ord-c986ea5d580242699b99239ec61a45b1
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09334279B2

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