Acetonitrile → (2S,4S)-4-Fluoro-1-[({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}amino)acetyl]pyrrolidine-2-carbonitrile hydrochloride

HRID 350857

Reaktionsgleichung

Reaktionsgleichung von HRID 350857
[ClH:1].[F:2][C:3]([F:18])([F:17])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.Br[CH2:20][C:21]([N:23]1[CH2:27][C@@H:26]([F:28])[CH2:25][C@H:24]1[C:29]#[N:30])=[O:22].C(N(CC)CC)C.C(#N)C>Cl.O1CCOCC1.CC(C)=O.CCOCC>[ClH:1].[F:28][C@@H:26]1[CH2:27][N:23]([C:21](=[O:22])[CH2:20][NH:16][CH:13]2[CH2:14][CH2:15][N:10]([C:7]3[CH:6]=[CH:5][C:4]([C:3]([F:2])([F:17])[F:18])=[CH:9][CH:8]=3)[CH2:11][CH2:12]2)[C@H:24]([C:29]#[N:30])[CH2:25]1

Komponenten

8

Edukt 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 210903881-(4-(Trifluoromethyl)phenyl)piperidin-4-amine hydrochlorideHCID 21090395(2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile

Produkt 1

HCID 69515823(2S,4S)-4-Fluoro-1-[({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}amino)acetyl]pyrrolidine-2-carbonitrile hydrochlorideAusbeute 47,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidKatalysatorHCID 312751,4-DioxaneLösungsmittelHCID 21584533Acetone diethyletherLösungsmittel

Versuchsvorschrift

A round bottom flask was mixed with 1-[4-(trifluoromethyl)phenyl]piperidin-4-amine hydrochloride (337 mg, 1.34 mmol), (2S,4S)-1-(bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (316 mg, 1.34 mmol), trietylamine (408 mg, 04.03 mmol) and acetonitrile (20 mL). The reaction mixture was allowed to stir at RT for 17.0 hours. The reaction mixture was concentrated to dryness. The reaction mixture was partitioned between EtOAc and saturated NaHCO3 and the organics were dried over MgSO4. The organics were concentrated to dryness and dried in vacuo. The resulting crude solid was purified using silica gel chromatography (99% CH2Cl2/1% MeOH, with 1.7% NH3) to yield a pure solid. The solid was dissolved into a 1/1 acetone/ether solution and mixed with several drops of 4.0 N HCl in 1,4-dioxane. The resulting solid was filtered and dried in vacuo to give a total of 277 mg of pure solid.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customThe reaction mixture was partitioned between EtOAc and saturated NaHCO3
  3. dry with materialthe organics were dried over MgSO4
  4. concentrationThe organics were concentrated to dryness
  5. customdried in vacuo
  6. customThe resulting crude solid was purified
  7. customto yield a pure solid
  8. filtrationThe resulting solid was filtered
  9. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-7c0757c11a3c4bd28b83561237d1abcd
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07183290B2

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