Ammonium Chloride → HCID 131723345, compound

HRID 2188391Notes

Reaction equation

HRID 2188391 reaction equation
[Mg].[F:2][C:3]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:4]=1[CH2:5]Br.[CH3:12][N:13]([CH:15]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C:17]1=[O:22])[CH3:14].[Cl-:29].[NH4+]>CCOCC>[ClH:29].[F:2][C:3]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:4]=1[CH2:5][C:17]1([OH:22])[CH2:18][CH2:19][CH2:20][CH2:21][CH:16]1[CH:15]([N:13]([CH3:12])[CH3:14])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 5462224MagnesiumHCID 111722992-(Dimethylaminophenylmethyl)cyclohexanone

Product 1

HCID 131723345HCID 131723345, compoundYield 32.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

0.29 g (11.9 mmole) of magnesium turnings was stirred in 5 ml of ether of analysis purity. 2.47 g (11.9 mmole) of 2,4-difluorobenzyl bromide dissolved in 10 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. 2.30 g (9.9 mmole) of the 2-(dimethylaminophenylmethyl)cyclohexanone prepared according to Example 1 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 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). 1.78 g of crude base (49.9% of theory) were obtained. The aqueous solution was extracted three times with 15 ml of ether and 15 ml of dichloromethane each time. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 1.31 g of crude base (36.7% of theory) were obtained. The hydrochloride was precipitated from both bases according to Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone. 0.95 g of 1-(2,4-difluorobenzyl)-2-(dimethylaminophenylmethyl)cyclohexanol, hydrochloride (20.2% of theory) was obtained from the first base, and 1.27 g of 1-(2,4-difluorobenzyl)-2-(dimethylaminophenylmethyl)cyclohexanol, hydrochloride (32.4% of theory) with a melting point of 178° C. was obtained from the second base.

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. extractionextracted 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. custom1.78 g of crude base (49.9% of theory) were obtained
  11. extractionThe aqueous solution was extracted three times with 15 ml of ether and 15 ml of dichloromethane each time
  12. dry with materialThe combined organic extracts were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated by evaporation on a rotary evaporator (500 to 10 mbar)
  15. custom1.31 g of crude base (36.7% of theory) were obtained
  16. customThe hydrochloride was precipitated from both bases

Sources & evidence

ORD record
ord-ce2567911d214ea9801299cadecc48bf
Source dataset
uspto-grants-2002_06
Patent number
US06410790B1

Reaction notes

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