Ammonium Chloride → 1-[4-(Hydroxy-3,3,5,5-tetramethylcyclohexyl)phenyl]ethanone

HRID 1071916Notes

Reaction equation

HRID 1071916 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]([O:17]C)(OC)[CH3:14])=[CH:9][CH:8]=1.[CH3:19][C:20]1([CH3:29])[CH2:25][C:24]([CH3:27])([CH3:26])[CH2:23][C:22](=[O:28])[CH2:21]1.[Cl-].[NH4+]>CCCCCC.O1CCCC1>[OH:28][C:22]1([C:7]2[CH:8]=[CH:9][C:10]([C:13](=[O:17])[CH3:14])=[CH:11][CH:12]=2)[CH2:23][C:24]([CH3:27])([CH3:26])[CH2:25][C:20]([CH3:29])([CH3:19])[CH2:21]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 843993,3,5,5-TetramethylcyclohexanoneHCID 109117821-Bromo-4-(1,1-dimethoxyethyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 223904201-[4-(Hydroxy-3,3,5,5-tetramethylcyclohexyl)phenyl]ethanoneYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

27.5 ml of a 1.6 M solution of n-butyllithium in hexane are added dropwise at −78° C. to a solution of 10 g of 1-bromo-4-(1,1-dimethoxyethyl)benzene (compound Vp) in 100 ml of tetrahydrofuran. The reaction mixture is stirred for 2 hours at this temperature. A solution of 6.92 ml of 3,3,5,5-tetramethylcyclohexanone in 20 ml of tetrahydrofuran is added over 20 minutes and the reaction mixture is stirred at −78° C. for 1 hour. After warming to room temperature, 140 ml of saturated aqueous ammonium chloride solution are added. The phases are separated after settling has taken place, the aqueous phase is extracted with diethyl ether, the organic phases are combined and dried over magnesium sulphate, and the solvents are evaporated off under reduced pressure. The oil obtained is purified by chromatography on a column of silica gel, eluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture; yield=88%; m.p.=135° C. The following compounds are prepared in the same way:

Workup

  1. stirringthe reaction mixture is stirred at −78° C. for 1 hour
  2. customThe phases are separated after settling
  3. extractionthe aqueous phase is extracted with diethyl ether
  4. dry with materialdried over magnesium sulphate
  5. customthe solvents are evaporated off under reduced pressure
  6. customThe oil obtained
  7. customis purified by chromatography on a column of silica gel
  8. washeluting with a 95/5 (v/v) cyclohexane/ethyl acetate mixture
  9. customThe following compounds are prepared in the same way

Sources & evidence

ORD record
ord-5460a4871551449fa5fe5f6c1f2cdb05
Source dataset
uspto-grants-2005_06
Patent number
US06908914B1

Reaction notes

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