Triethylamine → (S)-tert-butyl 2-((1R,2R)-3-(((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidine-1-carboxylate

HRID 74771Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 74771
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([O:19][CH3:20])[C@@H:14]([CH3:18])[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=N[C:31]2[CH:32]=[CH:33][CH:34]=N[C:30]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([N:47]([CH2:50][CH3:51])CC)C.C([O:55][CH2:56][CH3:57])(=O)C>ClCCl.CN(C)C=O>[OH:55][C@@H:56]([C:57]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C@H:50]([NH:47][C:15](=[O:17])[C@H:14]([CH3:18])[C@H:13]([C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[O:19][CH3:20])[CH3:51]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11033491(2R,3R)-3-((2S)-1-(tert-Butoxycarbonyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanoic acid

Produkt 1

HCID 20777964(S)-tert-butyl 2-((1R,2R)-3-(((1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidine-1-carboxylateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of #11 (2.00 g, 6.96 mmol, 1 eq.) in dichloromethane (21 mL, 0.3 M) and N,N-dimethylformamide (3 mL) was added HATU (3270 mg, 8.35 mmol, 1.2 eq.). After two minutes, the amine (1R,2S)-(+)-norephedrine (1.07 mg, 6.96 mmol, 1 eq.) and triethylamine (1.94 mL, 13.9 mmol, 2 eq.) were added. After two hours, the reaction mixture was diluted with ethyl acetate (100 mL), washed with a 1 M aqueous solution of hydrochloric acid and with brine, dried over sodium sulfate, filtered, concentrated in vacuo, and purified by silica gel chromatography (Gradient: 0% to 60% ethyl acetate in heptane) to provide #109 (2.18 g, 74%) as a white solid. LC-MS: m/z 321.3 [(M−Boc)+H+], retention time=3.14 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ 7.64 (d, J=8.6 Hz, 1H), 7.24-7.33 (m, 4H), 7.15-7.21 (m, 1H), 5.35 (br d, J=5 Hz, 1H), 4.45 (br dd, J=5, 5 Hz, 1H), 3.91-4.00 (m, 1H), 3.30-3.39 (m, 1H), 3.26 (s, 3H), 2.94-3.07 (m, 1H), 2.04-2.14 (m, 1H), 1.46-1.78 (m, 4H), 1.40 (s, 9H), 0.97-1.04 (m, 6H).

Aufarbeitung

  1. waitAfter two hours
  2. washwashed with a 1 M aqueous solution of hydrochloric acid and with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by silica gel chromatography (Gradient: 0% to 60% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-cd010eb1790c41f0a17ed4b92369a921
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828401B2

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