Triethylamine → 2-(3,5-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963320Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1963320
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([F:23])[CH:22]=1)[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.CC(OC)(C)C>C(#N)C.O>[F:23][C:21]1[CH:20]=[C:4]([CH:3]=[C:2]([F:1])[CH:22]=1)[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]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 15413tert-Butyl methyl etherHCID 82050Lithium BromideHCID 66734958Dimethyl 2-(3,5-difluorobenzyl)piperidine-1,4-dicarboxylate

Produkt 1

HCID 667322412-(3,5-Difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acidAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

Dimethyl 2-(3,5-difluorobenzyl)piperidine-1,4-dicarboxylate (8.459 g, 25.84 mmol) was dissolved in acetonitrile (85 mL) and water (1.7 mL). Lithium bromide (17.95 g, 206.74 mmol) and triethylamine (14.33 mL, 103.37 mmol) were added. The suspension was heated to reflux 1.5 h before water (100 mL) and MTBE (300 mL) were added. The organic phase was extracted with water (×2). The combined water phases were acidified to pH 1 with 3.8 M HCl and extracted with MTBE (×2). The combined organic phases were washed with water, dried with MgSO4, filtered through celite and concentrated. The crude product was redissolved in MTBE and washed with 0.1 M HCl (×2) and water. The organic phase was dried with MgSO4 and concentrated to give 2-(3,5-difluorobenzyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (6.88 g, 85%). MS m/z 314 (M+H)+

Aufarbeitung

  1. temperatureThe suspension was heated
  2. additionwere added
  3. extractionThe organic phase was extracted with water (×2)
  4. extractionextracted with MTBE (×2)
  5. washThe combined organic phases were washed with water
  6. dry with materialdried with MgSO4
  7. filtrationfiltered through celite
  8. concentrationconcentrated
  9. dissolutionThe crude product was redissolved in MTBE
  10. washwashed with 0.1 M HCl (×2) and water
  11. dry with materialThe organic phase was dried with MgSO4
  12. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-71881befdbc6466ca158a8b57cc2677b
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415378B2

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