3-Bromoanisole → 2-((Dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol

HRID 1837837Notes

Reaction equation

HRID 1837837 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([O:13][CH3:14])[CH:10]=[CH:11][CH:12]=1.[CH3:15][N:16]([CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C:20]1=[O:25])[CH3:17]>O1CCCC1.[Fe](Cl)(Cl)Cl>[CH3:17][N:16]([CH2:18][CH:19]1[C:20]([OH:25])([C:7]2[CH:8]=[C:9]([O:13][CH3:14])[CH:10]=[CH:11][CH:12]=2)[CH2:21][CH2:22][CH2:23][CH2:24]1)[CH3:15]

Participants

6

Reactant 3

HCID 169713-BromoanisoleHCID 858382-((Dimethylamino)methyl)cyclohexanoneHCID 178418339Butyllithium

Product 1

HCID 55232-((Dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanolYield 68.3%

Reagents, catalysts & solvents 2

HCID 24380Iron chloride (FeCl3)CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To 230 mL of anhydrous tetrahydrofuran (THF) cooled to −60° C. was added 9.36 g of n-butyl lithium (0.123 mol, 10 M solution in hexanes). The resulting yellow solution was stirred for 10 min and then 23.06 g of neat 3-bromoanisole (0.34 mol) was added dropwise with stirring. The resulting white suspension was stirred for 15 min. To the white suspension was then added dropwise, over a 4 hour period, a solution of 19.14 g of (±) 2-((dimethylamino)methyl)cyclohexanone (0.123 mol) and 400 mg of iron (III) chloride (2.5 mmol, 2 mol percent) in 190 mL of anhydrous THF at −60° C. The resulting reaction mixture was quenched with water, the organic phase was separated, the aqueous phase was extracted twice with diethyl ether and the diethyl ether extracts were combined. The combined ether extracts were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure to provide 37.77 g (0.084 mol, 68% yield) of the above-titled mixture in a ratio of 91.9:8.1 as determined using HPLC.

Workup

  1. stirringwith stirring
  2. stirringThe resulting white suspension was stirred for 15 min
  3. additionTo the white suspension was then added dropwise, over a 4 hour period
  4. customat −60° C
  5. customThe resulting reaction mixture
  6. customwas quenched with water
  7. customthe organic phase was separated
  8. extractionthe aqueous phase was extracted twice with diethyl ether
  9. dry with materialThe combined ether extracts were dried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-97d064e5829f4bf89ad0f98971d2346b
Source dataset
uspto-grants-2004_08
Patent number
US06784319B2

Reaction notes

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