Triethylamine → HCID 66681429, Verbindung

HRID 339641

Reaktionsgleichung

Reaktionsgleichung von HRID 339641
Cl.[CH:2]1([CH2:5][NH:6][C:7](=[O:15])[CH:8]=[C:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[F:23][C:24]([F:35])([F:34])[C:25]([C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)=O.C([BH3-])#N.[Na+]>C(Cl)Cl.CO.Cl[Ti](Cl)(Cl)Cl>[CH:2]1([CH2:5][NH:6][C:7](=[O:15])[CH:8]=[C:9]2[CH2:14][CH2:13][N:12]([CH:25]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:24]([F:23])([F:35])[F:34])[CH2:11][CH2:10]2)[CH2:4][CH2:3]1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 695642,2,2,4'-TetrafluoroacetophenoneHCID 5003444Sodium cyanoborohydrideHCID 66680987N-(cyclopropylmethyl)-2-(piperidin-4-ylidene)acetamide hydrochloride

Produkt 1

HCID 66681429HCID 66681429, VerbindungAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24193Titanium TetrachlorideKatalysatorHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A solution of TiCl4 (0.0299 ml, 0.271 mmol) in CH2Cl2 (0.5 ml) was added to a solution of N-(cyclopropylmethyl)-2-(piperidin-4-ylidene)acetamide hydrochloride (125 mg, 0.542 mmol) prepared in EXAMPLE 22e, triethylamine (0.225 ml, 1.63 mmol) and 2,2,2,4′-tetrafluoroacetophenone (0.0770 ml, 0.542 mmol) in CH2Cl2 (3.5 ml), and the whole was stirred for 9 hours. A solution of sodium cyanoborohydride (102 mg, 1.63 mmol) in methanol (1 ml) was added to the reaction mixture and the whole was stirred for 30 minutes. After the reaction was quenched with aqueous 2 N NaOH solution (15 ml), the aqueous phase was extracted with ethyl acetate (30 ml×2) and the combined organic phase was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/n-hexane: 35/65 to 55/45) to give N-(cyclopropylmethyl)-2-(1-(2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)piperidin-4-ylidene)acetamide (52 mg, 26%) as a yellow solid: LCMS: 371 {M+1}+. 1H NMR (DMSO-d6)□ δ: 0.11 (m, 2H), 0.37 (m, 2H), 0.85 (m, 1H), 2.17 (m, 2H), 2.43-2.68 (m, 4H), 2.91 (m, 4H), 4.70 (m, 1H), 5.57 (s, 1H), 7.26 (m, 2H), 7.45 (m, 2H), 7.87 (t, 1H).

Aufarbeitung

  1. stirringthe whole was stirred for 30 minutes
  2. customAfter the reaction was quenched with aqueous 2 N NaOH solution (15 ml)
  3. extractionthe aqueous phase was extracted with ethyl acetate (30 ml×2)
  4. dry with materialthe combined organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (ethyl acetate/n-hexane: 35/65 to 55/45)

Quellen und Nachweise

ORD-Eintrag
ord-e27e3498ea2a460abf06d6052f51e120
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895551B2

Verknüpfte Notizen

Wird geladen…