1,2-Dichloro-4-fluorobenzene → 4-(3,4-Dichlorophenoxy)-[1,4']bipiperidinyl-1'-carboxylic acid tert-butyl ester

HRID 1060807Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1060807
CC(C)([O-])C.[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([N:20]2[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[Cl:27][C:28]1[CH:29]=[C:30](F)[CH:31]=[CH:32][C:33]=1[Cl:34].C([O-])(O)=O.[Na+]>C1COCC1.C(Cl)Cl>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([N:20]2[CH2:21][CH2:22][CH:23]([O:26][C:31]3[CH:30]=[CH:29][C:28]([Cl:27])=[C:33]([Cl:34])[CH:32]=3)[CH2:24][CH2:25]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Komponenten

7

Edukt 4

HCID 740281,2-Dichloro-4-fluorobenzeneHCID 516892Sodium BicarbonateHCID 9835508tert-Butyl 4-hydroxy-[1,4'-bipiperidine]-1'-carboxylateHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 112125444-(3,4-Dichlorophenoxy)-[1,4']bipiperidinyl-1'-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of potassium tert-butoxide (139.0 g, 1.24 mol) in THF (500 ml) was added a solution of the product of Step 1 (176.2 g, 0.62 mol) in THF (1000 ml). The reaction mixture was stirred 10 minutes before the additon of 3,4 dichlorofluorobenzene (122.8 g, 0.74 mol), this caused a green colouration that subsequently faded. The reaction mixture was then heated at reflux for 90 minutes. The reaction mixture was then cooled to room temperature before the addition of saturated NaHCO3 (1600 ml). The layers were separated and the organic layer stripped to leave an orange semi-solid. The solid was dissolved in DCM (1500 ml) and dried (MgSO4), filtered and the solvent removed. To the resultant solid was added methyl tert-butyl ether (MTBE) (54 ml) and iso-hexane (1000 ml) to give a slurry which was stirred overnight. The slurry was then filtered and washed with isohexane (200 ml) and the solid dried in vacuo at 50° C. to give the sub-titled compound as a pale powder, (211.6 g, 80%; MS: (M+H) 429).

Aufarbeitung

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux for 90 minutes
  3. customThe layers were separated
  4. customto leave an orange semi-solid
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed
  8. additionTo the resultant solid was added methyl tert-butyl ether (MTBE) (54 ml) and iso-hexane (1000 ml)
  9. customto give a slurry which
  10. filtrationThe slurry was then filtered
  11. washwashed with isohexane (200 ml)
  12. customthe solid dried in vacuo at 50° C.

Quellen und Nachweise

ORD-Eintrag
ord-9e1f6c508a3f48009a26ae6aa0808a6b
Quelldatensatz
uspto-grants-2003_02
Patentnummer
US06525070B2

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