Ammonium Chloride → HCID 23149957, compound

HRID 1670758Notes

Reaction equation

HRID 1670758 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CCCCCC.C([Li])CCC.C(OC([N:31]1[CH2:36][CH2:35][CH2:34][C:33](=[O:37])[CH2:32]1)=O)(C)(C)C.[Cl-].[NH4+]>C(OCC)C>[ClH:12].[Cl:12][C:5]1[CH:4]=[CH:3][C:2]([C:33]2([OH:37])[CH2:34][CH2:35][CH2:36][NH:31][CH2:32]2)=[CH:7][C:6]=1[C:8]([F:11])([F:10])[F:9]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 679594-Bromo-2-chloro-alpha,alpha,alpha-trifluorotolueneHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 178418244HCID 178418244, compound

Product 1

HCID 23149957HCID 23149957, compoundYield 53.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

5-Bromo-2-chlorobenzotrifluoride (Aldrich Co., 2.0 g) was dissolved in diethyl ether (50 ml), and the mixture was cooled to −78° C. An n-butyllithium hexane solution (2.6 M, 3.2 ml) was added to the solution and the mixture was stirred for 10 min. 1-(tert-Butoxycarbonyl)-3-piperidone (Aldrich Co., 1.6 g) was added, and the mixture was gradually warmed to room temperature. After completion of the reaction, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with diethyl ether. The organic layer was dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1-2:1)). The intermediate was dissolved in ethyl acetate, and a 4N hydrochloric acid-ethyl acetate solution (3 ml) was added. The mixture was stirred at room temperature for 3 hr. After completion of the reaction, the solvent was evaporated under reduced pressure. The precipitated solid was collected by filtration to give 3-[4-chloro-3-(trifluoromethyl)phenyl]piperidin-3-ol hydrochloride (655 mg, yield 27%).

Workup

  1. temperaturethe mixture was gradually warmed to room temperature
  2. customAfter completion of the reaction
  3. extractionthe mixture was extracted with diethyl ether
  4. customThe organic layer was dried
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1-2:1))
  7. dissolutionThe intermediate was dissolved in ethyl acetate
  8. additiona 4N hydrochloric acid-ethyl acetate solution (3 ml) was added
  9. stirringThe mixture was stirred at room temperature for 3 hr
  10. customAfter completion of the reaction
  11. customthe solvent was evaporated under reduced pressure
  12. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-d7b793c906c64e4591d006c0fefd84ba
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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