Ammonium Chloride → 1-(4-Tert.-butylbenzyl)-2-[dimethylaminothiophen-2-ylmethyl]cyclo-hexanol, hydrochloride

HRID 2188415Notes

Reaction equation

HRID 2188415 reaction equation
[Mg].[C:2]([C:6]1[CH:13]=[CH:12][C:9]([CH2:10]Br)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3].[CH3:14][N:15]([CH:17]([C:25]1[S:26][CH:27]=[CH:28][CH:29]=1)[CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C:19]1=[O:24])[CH3:16].[Cl-:30].[NH4+]>CCOCC>[ClH:30].[C:2]([C:6]1[CH:13]=[CH:12][C:9]([CH2:10][C:19]2([OH:24])[CH2:20][CH2:21][CH2:22][CH2:23][CH:18]2[CH:17]([N:15]([CH3:14])[CH3:16])[C:25]2[S:26][CH:27]=[CH:28][CH:29]=2)=[CH:8][CH:7]=1)([CH3:5])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 878361-(Bromomethyl)-4-(1,1-dimethylethyl)benzeneHCID 5462224MagnesiumHCID 178011062-(Dimethylaminothiophen-2-ylmethyl)cyclohexanone

Product 1

HCID 98668911-(4-Tert.-butylbenzyl)-2-[dimethylaminothiophen-2-ylmethyl]cyclo-hexanol, hydrochlorideYield 26.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

0.31 g (12.6 mmole) of magnesium turnings was stirred in 10 ml of ether of analysis purity. 2.30 g (12.6 mmole) of 4-tert.-butylbenzyl 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. 2.50 g (10.5 mmole) of the 2-(dimethylaminothiophen-2-ylmethyl)cyclohexanone prepared according to Example 70 were dissolved in 10 ml of ether, added dropwise to the Grigiard reagent while cooling in all 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 with 20 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). 3.69 g of crude base (90.7% of theory) were obtained, from which 1.16 g of 1-(4-tert.-butylbenzyl)-2-[dimethylaminothiophen-2-ylmethyl]cyclo-hexanol, hydrochloride (26.2% 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 210° C.

Workup

  1. additionwere added dropwise so that the reaction mixture
  2. additionAfter completion of the addition the reaction mixture
  3. additionadded dropwise to the Grigiard reagent
  4. temperaturewhile cooling in all ice bath
  5. stirringstirred for 15 hours at RT
  6. temperaturewhile cooling in an ice bath
  7. extractionwas extracted three times at RT with 20 ml of ether each time
  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-06354f6fe7aa456785b27543144bfec1
Source dataset
uspto-grants-2002_06
Patent number
US06410790B1

Reaction notes

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