Diisopropylethylamine → 2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide

HRID 15285

Reaktionsgleichung

Reaktionsgleichung von HRID 15285
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:21][C@@H:22]([CH:25]([CH3:27])[CH3:26])[CH2:23][OH:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CCCCCC.CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[C:9]([NH:21][C@H:22]([CH2:23][OH:24])[CH:25]([CH3:27])[CH3:26])=[O:11])=[CH:6][CH:7]=1

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 640993L-ValinolHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 684826142-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid

Produkt 1

HCID 684813832-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramideAusbeute 41 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 8058HexaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

2-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid (2.00 g, 7.11 mmol, 1.0 eq.), 2-(S)-Amino-3-methyl-butan-1-ol (1.59 g, 7.33 mmol, 1.03 eq.) and HATU (2.41 g, 7.33 mmol, 1.03 mmol) were dissolved in CH2Cl2 and stirred at room temperature. Diisopropylethylamine (3.9 mL, 21.98 mmol, 3.1 eq.) was added via syringe and the reaction is monitored by LC/MS. Upon completion, there reaction was evaporated and is diluted with ethyl acetate (100 mL) and extracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine. The organic layer is dried over MgSO4, filtered and evaporated. Column chromatography (0-100%) EtOAc in hexane gradient provided 2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide as a clear oil (1.06 g, 2.89 mmol, 41%). HPLC-MS calcd. for C19H27FN2O4 (M+H+) 367.2, found 367.4; TLC (1:1 hexane/EtOAc) Rf=0.15.

Aufarbeitung

  1. customUpon completion, there reaction
  2. customwas evaporated
  3. additionis diluted with ethyl acetate (100 mL)
  4. extractionextracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine
  5. dry with materialThe organic layer is dried over MgSO4
  6. filtrationfiltered
  7. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-c742906c4d0441f186bd0d9a5f0ae671
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732449B2

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