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

HRID 1293526Notes

Reaction equation

HRID 1293526 reaction equation
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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

  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.

Sources & evidence

ORD record
ord-a5c5bee7283e4129a21c1ec3f888730b
Source dataset
uspto-grants-2007_07
Patent number
US07238811B2

Reaction notes

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