Carbon Dioxide → HCID 59331987, compound

HRID 2361833Notes

Reaction equation

HRID 2361833 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=2)([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[C:33](=[O:35])=[O:34]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:21]2[CH:26]=[CH:25][C:24]([C:33]([OH:35])=[O:34])=[CH:23][CH:22]=2)([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 280Carbon Dioxide2×HCID 57691398tert-Butyl 4-(4-bromophenyl)-4-(4-chlorophenyl)-piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 59331987HCID 59331987, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen, a solution of 4-(4-bromo-phenyl)-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester* (888 mg, 1.97 mmol) in THF (5 mL) was cooled to −78° C. A solution of n-butyllithium (1.5 mL, 1.6M in hexanes) was added dropwise and the mixture maintained at this temperature for 25 minutes. Carbon dioxide gas (generated from dry ice and dried by passage through a column of calcium chloride pellets) was bubbled through the anion solution for 80 minutes then the mixture was allowed to warm to room temperature. The solvents were removed in vacuo then the residue was partitioned between 1N hydrochloric acid and diethyl ether. The organic phase was separated, dried (MgSO4), filtered and concentrated. The combined aqueous phases were further extracted with ethyl acetate, this extract also being dried (MgSO4), filtered, combined with the ethereal extract and concentrated to afford 4-(4-carboxy-phenyl)-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (889 mg); LCMS (PS-A2) Rt 3.52 min [M−tBu+H]+ 360. *This starting material can be made by the method described in Example 14A followed by Example 48A

Workup

  1. temperaturethe mixture maintained at this temperature for 25 minutes
  2. dry with materialdried by passage through a column of calcium chloride pellets)
  3. customwas bubbled through the anion solution for 80 minutes
  4. customThe solvents were removed in vacuo
  5. customthe residue was partitioned between 1N hydrochloric acid and diethyl ether
  6. customThe organic phase was separated
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. extractionThe combined aqueous phases were further extracted with ethyl acetate
  11. extractionthis extract also
  12. dry with materialbeing dried (MgSO4)
  13. filtrationfiltered
  14. extractionextract
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-60f3ffceb8fc430eab7224f152cb33f0
Source dataset
uspto-grants-2014_04
Patent number
US08691806B2

Reaction notes

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