Ammonium Chloride → HCID 131723332, compound

HRID 2188377Notes

Reaction equation

HRID 2188377 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]2[O:8][CH2:9][O:10][C:4]=2[CH:3]=1.C([Li])CCC.[CH3:16][N:17]([CH:19]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=1)[CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][C:21]1=[O:26])[CH3:18].[Cl-:35].[NH4+]>O1CCCC1>[ClH:35].[O:8]1[C:5]2[CH:6]=[CH:7][C:2]([C:21]3([OH:26])[CH2:22][CH2:23][CH2:24][CH2:25][CH:20]3[CH:19]([N:17]([CH3:18])[CH3:16])[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=3)=[CH:3][C:4]=2[O:10][CH2:9]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 758311-Bromo-3,4-(methylenedioxy)benzeneHCID 22447829HCID 22447829, compoundHCID 178418339Butyllithium

Product 1

HCID 131723332HCID 131723332, compoundYield 43.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

2.61 g (13.0 mmole) of 4-bromo-1,2-methylenedioxybenzene were dissolved in 10 ml of tetrahydrofuran and cooled to −70° C. under nitrogen in a dry ice/isopropanol bath. 7.9 ml (13.0 mmole) of n-butyllithium (1.6 M in hexane) were added dropwise while stirring so that the temperature did not rise above −60° C. The reaction mixture was stirred for a further 30 minutes and then 3.0 g (10.8 mmole) of the 2-[dimethylamino-(3-methoxyphenyl)methyl]cyclohexanone prepared according to Example 9 and dissolved in 10 ml of tetrahydrofuran were added dropwise while cooling in an ice bath, and the whole was heated to RT within two hours. The reaction mixture was worked up by adding 20 ml of saturated ammonium chloride solution while cooling in an ice bath, and was extracted three times at RT, each time with 20 ml of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated by evaporation on a rotary evaporator (500 to 10 mbar). 4.10 g of crude base (98.8% of theory) were obtained, from which 1.96 g of 1-benzo[1,3]dioxol-5-yl-2-[dimethylamino-(3-methoxyphenyl)methyl]cyclohexanol, hydrochloride (43.2% of theory) were obtained according to the procedure described in Example 1 (3rd stage) with chlorotrimethylsilane/water in 2-butanone. The hydrochloride decomposes on heating above 109° C.

Workup

  1. customdid not rise above −60° C
  2. stirringThe reaction mixture was stirred for a further 30 minutes
  3. additionwere added dropwise
  4. temperaturewhile cooling in an ice bath
  5. temperaturethe whole was heated to RT within two hours
  6. temperaturewhile cooling in an ice bath
  7. extractionwas extracted three times at RT
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated by evaporation on a rotary evaporator (500 to 10 mbar)

Sources & evidence

ORD record
ord-687c7637e14040ea94a5452364eeab65
Source dataset
uspto-grants-2002_06
Patent number
US06410790B1

Reaction notes

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