Ammonium Chloride → HCID 70873515, compound

HRID 2172244Notes

Reaction equation

HRID 2172244 reaction equation
C([Mg]Cl)(C)C.I[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][C:34](=[O:37])[CH2:33][CH2:32]2)=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][C:34]([C:7]3[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=3)([OH:37])[CH2:33][CH2:32]2)=[CH:27][CH:26]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 21260565HCID 21260565, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 70873515HCID 70873515, compoundYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Isopropylmagnesium chloride (2M tetrahydrofuran solution) (11.73 ml) was added to a tetrahydrofuran solution (20 ml) of 4-iodobenzotrifluoride (3.45 ml, 23.5 mmol) dropwise at −10° C. under an argon atmosphere. The mixture was stirred at the same temperature for 5 minutes and further stirred at room temperature for 2 hours. After cooling the mixture to −10° C., a tetrahydrofuran solution (40 ml) of 1-(4-benzyloxyphenyl)piperidin-4-one (6 g, 21.3 mmol) was added thereto dropwise. While gradually returning to room temperature, the mixture was stirred. After 10 hours, a saturated ammonium chloride aqueous solution/ice water was poured into the mixture, followed by extraction with ethyl acetate. The result was washed with water and a saturated sodium chloride aqueous solution and dried over sodium sulfate. After removing the desiccant by filtration, the solvent was distilled off. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25→66:34). The resultant was washed with a mixed solvent of isopropyl ether and hexane and filtered to afford the title compound as a white powder (6.69 g, 73%).

Workup

  1. stirringfurther stirred at room temperature for 2 hours
  2. customWhile gradually returning to room temperature
  3. stirringthe mixture was stirred
  4. waitAfter 10 hours
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe result was washed with water
  7. dry with materiala saturated sodium chloride aqueous solution and dried over sodium sulfate
  8. customAfter removing the
  9. filtrationdesiccant by filtration
  10. distillationthe solvent was distilled off
  11. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25→66:34)
  12. washThe resultant was washed with a mixed solvent of isopropyl ether and hexane
  13. filtrationfiltered

Sources & evidence

ORD record
ord-5d635bdeb01743688d322cfe2a4f40de
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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