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

HRID 1837836Notes

Reaction equation

HRID 1837836 reaction equation
C([Li])(CC)C.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-]>[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

7

Reactant 3

HCID 169713-BromoanisoleHCID 858382-((Dimethylamino)methyl)cyclohexanone2×HCID 178418400CID 53628100

Product 1

HCID 55232-((Dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanolYield 89.2%

Reagents, catalysts & solvents 3

HCID 312ChlorideCatalystHCID 23925IronCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To 120 mL of anhydrous tetrahydrofuran (THF) cooled to −50° C. was added 400 mL of sec-butyl lithium (0.52 mol, 1.3 M solution in cyclohexane). The resulting yellow suspension was stirred for 10 min and then 63.56 g of neat 3-bromoanisole (0.34 mol) was added dropwise with stirring. The yellow suspension turned red, and then a white precipitate formed. The resulting white suspension was stirred for 30 min. In a separate vessel 52.75 g of (±) 2-((dimethylamino)methyl) cyclohexanone was dissolved in 107 mL of anhydrous THF at 0° C. To the resulting solution of (±) 2-((dimethylamino)methyl) cyclohexanone was added, dropwise with stirring, a solution of 1.03 g of iron (mH) chloride (6.3 mmol, 1 mol percent) in anhydrous THF. The resulting violet solution was transferred dropwise to the stirred white suspension at −50° C. using a metering pump. The resulting reaction mixture was quenched with 100 mL of water, the organic phase separated, the aqueous phase was extracted twice with 100 mL diethyl ether, and the diethyl ether extracts combined. The combined diethyl ether extracts were dried over sodium sulfate, filtered, and the diethyl ether solvent was removed under reduced pressure to provide 89.82 g (0.303 mol, 89% yield) of the above-titled mixture in a ratio of 93.9:6.1 as determined using HPLC.

Workup

  1. stirringwith stirring
  2. customa white precipitate formed
  3. stirringThe resulting white suspension was stirred for 30 min
  4. stirringdropwise with stirring
  5. customwas transferred dropwise to the stirred white suspension at −50° C.
  6. customThe resulting reaction mixture
  7. customwas quenched with 100 mL of water
  8. customthe organic phase separated
  9. extractionthe aqueous phase was extracted twice with 100 mL diethyl ether
  10. dry with materialThe combined diethyl ether extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. customthe diethyl ether solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-aa883897d7204a9bb3ffd900823c0bbd
Source dataset
uspto-grants-2004_08
Patent number
US06784319B2

Reaction notes

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