Tetrahydrofuran → HCID 10108892, compound

HRID 2244494Notes

Reaction equation

HRID 2244494 reaction equation
[Mg].BrCC[C:5]1C=C[CH:8]=[C:7]([F:11])[CH:6]=1.[CH2:12]([C:19]1([N:26]([CH3:28])[CH3:27])[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Cl-:29].[NH4+].O1[CH2:35][CH2:34][CH2:33][CH2:32]1>>[CH2:12]([C:19]1([N:26]([CH3:27])[CH3:28])[CH2:20][CH2:21][C:22]([CH2:32][CH2:33][C:34]2[CH:35]=[CH:8][C:7]([F:11])=[CH:6][CH:5]=2)([OH:25])[CH2:23][CH2:24]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[ClH:29].[CH2:12]([C:19]1([N:26]([CH3:27])[CH3:28])[CH2:20][CH2:21][C:22]([CH2:32][CH2:33][C:34]2[CH:35]=[CH:8][C:7]([F:11])=[CH:6][CH:5]=2)([OH:25])[CH2:23][CH2:24]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran3×HCID 25517Ammonium ChlorideHCID 5731291-(2-Bromoethyl)-3-fluorobenzeneHCID 5462224MagnesiumHCID 204534784-Benzyl-4-(dimethylamino)cyclohexanone

Product 2

HCID 10108892HCID 10108892, compoundHCID 10271798HCID 10271798, compound

Procedure

757 mg magnesium were stirred into 15 ml analytical grade tetrahydrofuran under a nitrogen atmosphere and approximately one third of the solution of 5.69 g 1-(2-bromoethyl)-3-fluorobenzene in 16 ml analytical grade tetrahydrofuran was added. The remainder of the solution was rapidly added dropwise after the Grignard formation had started, and when the addition had ended the mixture was subsequently stirred for one hour, 3.60 g 4-benzyl-4-dimethylaminocyclohexanone, dissolved in 16 ml analytical grade tetrahydrofuran, were then added dropwise and the reaction mixture was stirred overnight. For working up, 31 ml ammonium chloride solution (20 per cent by weight) were added, while cooling with ice, the phases were separated, the aqueous phase was extracted twice with 40 ml diethyl ether each time, the combined organic phases were washed with 30 ml water and extracted three times with 40 ml dilute hydrochloric acid (5 per cent by weight) each time, the combined aqueous extracts were washed with 30 ml diethyl ether, adjusted to pH 9 with ammonia solution (25 per cent by weight) and extracted three times with 40 ml methylene chloride each time, the combined methylene chloride extracts were dried over sodium sulfate, filtered and concentrated and the residue was largely freed from solvent residues in vacuo. The crude product obtained (3.96 g) was chromatographed over silica gel with diethyl ether/hexane (v/v=1:1). 301 mg of the nonpolar diastereoisomer of 4-benzyl-4-dimethylamino-1[2-(4-fluorophenyl)ethyl]cyclohexanol were obtained, from which 254 mg of the corresponding hydrochloride were prepared as described for example 4.

Workup

  1. additionThe remainder of the solution was rapidly added dropwise after the Grignard formation
  2. additionwhen the addition
  3. additionwere then added dropwise
  4. stirringthe reaction mixture was stirred overnight
  5. temperaturewhile cooling with ice
  6. customthe phases were separated
  7. extractionthe aqueous phase was extracted twice with 40 ml diethyl ether each time
  8. washthe combined organic phases were washed with 30 ml water
  9. extractionextracted three times with 40 ml dilute hydrochloric acid (5 per cent by weight) each time
  10. washthe combined aqueous extracts were washed with 30 ml diethyl ether
  11. extractionextracted three times with 40 ml methylene chloride each time
  12. dry with materialthe combined methylene chloride extracts were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product obtained (3.96 g)
  16. customwas chromatographed over silica gel with diethyl ether/hexane (v/v=1:1)

Sources & evidence

ORD record
ord-f9fd8b899293406aaf19093df2538e3f
Source dataset
uspto-grants-2010_03
Patent number
US07678834B2

Reaction notes

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