1,2-Dichloroethane → N-[2-[(2R,4R)-4-Hydroxy-2-methylpyrrolidin-1-yl]-2-oxoethyl}-3-(trifluoromethyl)benzamide

HRID 2367025Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2367025
Cl.[CH3:2][C@H:3]1[NH:7][CH2:6][C@H:5]([OH:8])[CH2:4]1.C(N(C(C)C)CC)(C)C.[F:18][C:19]([F:34])([F:33])[C:20]1[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=1)[C:23]([NH:25][CH2:26][C:27](O)=[O:28])=[O:24].C(Cl)CCl>ClCCl.[NH4+].[Cl-].O.CO.C(OCC)(=O)C.C(OCC)(=O)C>[OH:8][C@H:5]1[CH2:6][N:7]([C:27](=[O:28])[CH2:26][NH:25][C:23](=[O:24])[C:22]2[CH:30]=[CH:31][CH:32]=[C:20]([C:19]([F:18])([F:34])[F:33])[CH:21]=2)[C@H:3]([CH3:2])[CH2:4]1

Komponenten

9

Edukt 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 67314837(3R,5R)-5-Methylpyrrolidin-3-ol hydrochloride

Produkt 1

HCID 57803302N-[2-[(2R,4R)-4-Hydroxy-2-methylpyrrolidin-1-yl]-2-oxoethyl}-3-(trifluoromethyl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 21584119Ethylacetate methanolLösungsmittelHCID 57429219Ammonium chloride monohydrateLösungsmittel

Versuchsvorschrift

(3R,5R)-5-Methylpyrrolidin-3-ol hydrochloride (1.80 g, 13 mmol) was dissolved in dichloromethane (50 mL) and diisopropylethylamine (2.1 mL, 12.0 mmol) under nitrogen. (3-Trifluoromethyl-benzoylamino)-acetic acid (2.93 g, 11.85 mmol) was added followed by EDC (3.41 g, 17.8 mmol) and the mixture was stirred at room temperature for four hours. The mixture was diluted with NH4Cl/H2O and extracted twice with ethyl acetate. The combined extracts were washed with NaHCO3/H2O and brine, dried over MgSO4, filtered and concentrated to give a dark orange oil. Chromatography on silica gel eluting with ethyl acetate to 5% methanol/ethyl acetate gave the coupled product as a pale orange solid, 3.19 g (81%, 2 steps). LC/MS (M+H)+ m/z=331.1. 1H NMR (CDCl3, major rotamer) δ 8.12 (s, 1H), 8.01 (d, 1H), 7.76 (d, 1H), 7.57 (t, 1H), 7.50 (m, 1H), 4.56 (m, 1H), 4.34 (m, 1H), 4.23 (m, 1H), 4.11 (m, 1H), 3.61 (dd, 1H), 3.51 (d, 1H), 2.71 (d, 1H), 2.17 (m, 1H), 1.81 (m, 1H), 1.32 (d, 3H).

Aufarbeitung

  1. extractionextracted twice with ethyl acetate
  2. washThe combined extracts were washed with NaHCO3/H2O and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a dark orange oil

Quellen und Nachweise

ORD-Eintrag
ord-3946e9f375bd41faa46fd327d83aadd0
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697870B2

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