4-Methylmorpholine → (R)-3-[3,5-dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(tetrahydro-pyran-4-yl)-pyrrolidin-2-one

HRID 416021Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 416021
[Cl:1][C:2]1[CH:3]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([OH:30])=O)=[CH:24][CH:23]=2)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:10]1=[O:20].Cl.[F:32][C:33]([F:41])([F:40])[CH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>ClCCl>[Cl:21][C:6]1[CH:5]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:37]3[CH2:38][CH2:39][CH:34]([C:33]([F:41])([F:40])[F:32])[CH2:35][CH2:36]3)=[O:30])=[CH:24][CH:23]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)[C:10]1=[O:20]

Komponenten

7

Edukt 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 66621883HCID 66621883, Verbindung

Produkt 1

HCID 24757987(R)-3-[3,5-dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(tetrahydro-pyran-4-yl)-pyrrolidin-2-oneAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Treat a solution of 3′,5′-dichloro-4′-[(R)-2-oxo-1-(tetrahydro-pyran-4-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (0.25 g, 0.56 mmol), 4-(trifluoromethyl)piperidine hydrochloride (0.13 g, 0.67 mmol), 1-hydroxybenzotriazole (0.23 g, 0.67 mmol), and 4-methylmorpholine (0.18 mL, 1.67 mmol) in dichloromethane (10 mL) with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.13 g, 0.67 mmol) and stir at room temperature for 6 hr. Quench the reaction with 1N hydrochloric acid and extract with ethyl acetate. Wash the organic layer with brine, dry over magnesium sulfate, and filter. Purify the crude material by silica gel column chromatography using hexanes:ethyl acetate to afford 0.23 g (72%) of desired product: MS (m/z): 583 (M+).

Aufarbeitung

  1. customQuench
  2. customthe reaction with 1N hydrochloric acid
  3. extractionextract with ethyl acetate
  4. washWash the organic layer with brine
  5. dry with materialdry over magnesium sulfate
  6. filtrationfilter
  7. customPurify the crude material by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-34d55f94c3c741b7b5464b90ddd3223d
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08088776B2

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