Adamantanone → [(3-Tert-butyldimethylsilyloxy-4-methoxyphenyl)methoxy methylene]adamantane

HRID 974719Notes

Reaction equation

HRID 974719 reaction equation
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[C:2]1=O)[CH2:8]2.[Si:12]([O:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[C:23]([O:25][CH3:26])=O)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1.[Cl-].[Cl-].[Cl-].[Ti+3]>[Si:12]([O:19][C:20]1[CH:21]=[C:22]([CH2:23][O:25][CH:26]=[C:2]2[CH:3]3[CH2:9][CH:7]4[CH2:6][CH:5]([CH2:10][CH:1]2[CH2:8]4)[CH2:4]3)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 64151AdamantanoneHCID 11335452Methyl 3-tert-butyldimethylsilyloxy-4-methoxybenzoateHCID 21226445Aluminium lithium hydride

Product 1

HCID 19969138[(3-Tert-butyldimethylsilyloxy-4-methoxyphenyl)methoxy methylene]adamantaneYield 20.9%

Reagents, catalysts & solvents 2

HCID 10313229titanium(III) trichlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

2-Adamantanone (Aldrich, 55 mg, 0.37 mmol) and methyl 3-tert-butyldimethylsilyloxy-4-methoxybenzoate (90 mg, 0.30 mmol, prepared as in Step 2, above) were mixed and dissolved in 0.9 ml of anhydrous tetrahydrofuran (THF). Lithium aluminum hydride (51 mg, 1.34 mmol) was added with stirring to an ice-cold mixture of titanium trichloride (Aldrich, 440 mg, 2.85 mmol) in THF under nitrogen. The ice-bath was removed and triethylamine was added to the mixture. After refluxing for 1 hr, the 2-adamantanone-methyl3-tert-butyldimethylsilyloxy-4-methoxybenzoate mixture was introduced via a syringe pump over 5 hr period. The mixture was refluxed and stirred for 4 additional hours. After cooling to room temperature, the black mixture was partitioned three times between saturated sodium bicarbonate solution and ethyl acetate. The combined extracts were washed with water and brine and dried over magnesium sulfate. The solution was evaporated to give a tan solid which was flash-chromatographed over silica gel. Elution with hexane/ethylacetate (15:1) afforded 26 mg of [(3-tert-butyldimethylsilyloxy-4-methoxyphenyl)methoxy methylene]adamantane as a colorless oil. NMR(δ):0.18 (s,6H),1.00 (s,9H),3.30 (s,3H),3.85 (s,3H).

Workup

  1. customThe ice-bath was removed
  2. additiontriethylamine was added to the mixture
  3. temperatureAfter refluxing for 1 hr
  4. additionthe 2-adamantanone-methyl3-tert-butyldimethylsilyloxy-4-methoxybenzoate mixture was introduced via a syringe pump over 5 hr period
  5. temperatureThe mixture was refluxed
  6. customthe black mixture was partitioned three times between saturated sodium bicarbonate solution and ethyl acetate
  7. washThe combined extracts were washed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. customThe solution was evaporated
  10. customto give a tan solid which
  11. customwas flash-chromatographed over silica gel
  12. washElution with hexane/ethylacetate (15:1)

Sources & evidence

ORD record
ord-3c9fab6f606e427097c099729ffb26d4
Source dataset
uspto-grants-1997_03
Patent number
US05607625

Reaction notes

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