Ammonium Chloride → HCID 131723350, compound

HRID 2188400Notes

Reaction equation

HRID 2188400 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([N:28]([CH3:30])[CH3:29])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C:22]2=[O:27])=[CH:16][CH:15]=1.[Cl-].[NH4+]>CCOCC>[ClH:13].[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([CH:20]([N:28]([CH3:30])[CH3:29])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C:22]2([C:3]2[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=2)[OH:27])=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 5462224MagnesiumHCID 69943418HCID 69943418, compound

Product 1

HCID 131723350HCID 131723350, compoundYield 11.9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

0.22 g (9.0 mmole) of magnesium turnings was stirred in 5 ml of ether of analysis purity. 2.03 g (9.0 mmole) of 4-bromo-benzotrifluoride dissolved in 5 ml of ether were added dropwise so that the reaction mixture boiled gently. After completion of the addition the reaction mixture was stirred for a further hour at RT. 2.00 g (7.5 mmole) of the 2-[(4-chloro-phenyl)dimethylaminomethyl]cyclohexanone prepared according to Example 58 were dissolved in 10 ml of ether, added dropwise to the Grignard reagent while cooling in an ice bath, and stirred for 15 hours at RT. The reaction mixture was worked up by adding 10 ml of saturated ammonium chloride solution while cooling in an ice bath, and was extracted three times at RT with 15 ml of ether each time. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 2.65 g of crude base (85.4% of theory) were obtained, from which a hydrochloride was precipitated according to Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone. The base was freed from the hydrochloride with 20 ml of water and 5 ml of ammonia solution (25 vol. %), extracted three times with 20 ml of ether each time, and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 0.50 g of crude base (16.2% of theory) was obtained, from which 0.20 g of 2-[(4-chlorophenyl)dimethylaminomethyl]-(4-trifluoromethylphenyl)cyclohexanol, hydrochloride (6.0% of theory) with a melting point above 240° C. was obtained according to the procedure described in Example 1 (3rd Stage) with chlorotrimethylsilane/water in 2-butanone.

Workup

  1. additionwere added dropwise so that the reaction mixture
  2. additionAfter completion of the addition the reaction mixture
  3. temperaturewhile cooling in an ice bath
  4. stirringstirred for 15 hours at RT
  5. temperaturewhile cooling in an ice bath
  6. extractionwas extracted three times at RT with 15 ml of ether each time
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by evaporation on a rotary evaporator (500 to 10 mbar)
  10. custom2.65 g of crude base (85.4% of theory) were obtained, from which a hydrochloride
  11. customwas precipitated
  12. extractionextracted three times with 20 ml of ether each time
  13. dry with materialthe combined organic extracts were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated by evaporation on a rotary evaporator (500 to 10 mbar)

Sources & evidence

ORD record
ord-3e7eb846b3944bc6839f8f1d4aeb5ff9
Source dataset
uspto-grants-2002_06
Patent number
US06410790B1

Reaction notes

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