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Triethylamine → 2-(3-Fluoro-4-(trifluoromethyl)benzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963334
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1963334
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[C:23]([F:26])([F:25])[F:24])[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([O:14]C)=[O:13])[CH2:9][CH2:8][N:7]1[C:16]([O:18][CH3:19])=[O:17].[Br-].[Li+].C(N(CC)CC)C>C(#N)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[C:23]([F:26])([F:24])[F:25])[CH2:5][CH:6]1[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9][CH2:8][N:7]1[C:16]([O:18][CH3:19])=[O:17]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 82050Lithium BromideHCID 66734842Dimethyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidine-1,4-dicarboxylate

Produkt 1

HCID 667322622-(3-Fluoro-4-(trifluoromethyl)benzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962
Water
Lösungsmittel
2×
HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of dimethyl 2-(3-fluoro-4-(trifluoromethyl)benzyl)piperidine-1,4-dicarboxylate (7.17 g, 19.00 mmol) in acetonitrile (60 mL) and water (1.2 mL) was added lithium bromide (13.20 g, 152.02 mmol) and triethylamine (10.54 mL, 76.01 mmol). The resulting mixture was heated under reflux for 2 h, then cooled to room temperature. Water was added and acetonitrile removed by evaporation. The aqueous layer was further diluted with water, then washed with MTBE. The organic layer was extracted with water. The combined aqueous layers were acidified with 3.8 M HCl, a colorless precipitate formed. The solids were extracted with DCM 6 times. The aqueous layer was extracted twice again with DCM. The combined organic layers were dried over MgSO4 and evaporated. 2-(3-Fluoro-4-(trifluoromethyl)benzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (6.56 g, 95%) was isolated as an off-white solid. MS m/z 364 (M+H)+

Aufarbeitung

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 2 h
  3. customacetonitrile removed by evaporation
  4. additionThe aqueous layer was further diluted with water
  5. washwashed with MTBE
  6. extractionThe organic layer was extracted with water
  7. customa colorless precipitate formed
  8. extractionThe solids were extracted with DCM 6 times
  9. extractionThe aqueous layer was extracted twice again with DCM
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-f371030e65bc42adbd915fd3ffd5d920
Quelldatensatz
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08415378B2

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