Cycloheptanone → 1-{4-[1-Ethyl-1-(4-hydroxy-3-methyl-phenyl)-propyl]-2-methyl-phenylethynyl}-cycloheptanol

HRID 547031Notes

Reaction equation

HRID 547031 reaction equation
C([Li])CCC.[CH2:6]([C:8]([C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([CH3:27])[CH:21]=1)([C:11]1[CH:16]=[CH:15][C:14]([C:17]#[CH:18])=[C:13]([CH3:19])[CH:12]=1)[CH2:9][CH3:10])[CH3:7].[C:28]1(=[O:35])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1.[Cl-].[NH4+]>O1CCCC1>[CH2:6]([C:8]([C:11]1[CH:16]=[CH:15][C:14]([C:17]#[C:18][C:28]2([OH:35])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[C:13]([CH3:19])[CH:12]=1)([C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([CH3:27])[CH:21]=1)[CH2:9][CH3:10])[CH3:7]

Participants

6

Reactant 4

HCID 10400CycloheptanoneHCID 25517Ammonium ChlorideHCID 585982954-[1-Ethyl-1-(4-ethynyl-3-methyl-phenyl)-propyl]-2-methyl-phenolHCID 178418339Butyllithium

Product 1

HCID 577090901-{4-[1-Ethyl-1-(4-hydroxy-3-methyl-phenyl)-propyl]-2-methyl-phenylethynyl}-cycloheptanolYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyllithium (1.59 M solution in hexane, 5.4 mL, 8.59 mmol) was added to a solution of 4-[1-ethyl-1-(4-ethynyl-3-methyl-phenyl)-propyl]-2-methyl-phenol (Example 1-(3); 1.00 g, 3.42 mmol) in tetrahydrofuran (15 mL) in a nitrogen atmosphere at 0° C., and the mixture was stirred for 15 minutes. Then, cycloheptanone (0.81 mL, 6.87 mmol) was added to the reaction mixture, which was stirred at 0° C. for one hour, heated to room temperature and further stirred for one hour. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=90:10 to 50:50) to give the target compound as a colorless oil (829 mg, 60%).

Workup

  1. stirringwas stirred at 0° C. for one hour
  2. stirringfurther stirred for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=90:10 to 50:50)

Sources & evidence

ORD record
ord-543c1a1bb41643a4b830c90b69e3ba54
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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