Ammonium Chloride → HCID 131723334, compound

HRID 2188379Notes

Reaction equation

HRID 2188379 reaction equation
[Mg].[CH3:2][O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7]Br.[CH3:12][N:13]([CH3:30])[CH:14]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)[CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C:16]1=[O:21].[Cl-:31].[NH4+]>CCOCC>[ClH:31].[CH3:30][N:13]([CH:14]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)[CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C:16]1([CH2:7][C:6]1[CH:9]=[CH:10][CH:11]=[C:4]([O:3][CH3:2])[CH:5]=1)[OH:21])[CH3:12]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 40672073-Methoxybenzyl bromideHCID 5462224MagnesiumHCID 22447829HCID 22447829, compound

Product 1

HCID 131723334HCID 131723334, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

0.32 g (13.0 mmole) of magnesium turnings was stirred in 10 ml of ether of analysis purity. 2.61 g (13.0 mmole) of 3-methoxybenzyl 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. 3.0 g (10.8 mmole) of the 2-[dimethyl-amino-(3-methoxyphenyl)methyl]cyclohexanone prepared according to Example 9 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 15 ml of saturated ammonium chloride solution while cooling in an ice bath, and was extracted three times at RT, each time with 15 ml of ether. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 3.87 g of crude base (101% 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 30 ml of water and 5 ml of ammonia solution (25 vol. %), extracted three times, each time with 15 ml of ether, and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 2.34 g of crude base (61.2% of theory) were obtained, from which 2.04 g of 2-[dimethylamino-(3-methoxyphenyl)methyl]-1-(3-methoxybenzyl)cyclohexanol, hydrochloride (48.4% of theory) were obtained according to Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone. The hydrochloride decomposes on heating above 75° C.

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
  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. custom3.87 g of crude base (101% of theory) were obtained, from which a hydrochloride
  11. customwas precipitated
  12. extractionextracted three times
  13. dry with materialeach time with 15 ml of ether, and the 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-2f4799b9338c4880ad07f05276cb085c
Source dataset
uspto-grants-2002_06
Patent number
US06410790B1

Reaction notes

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