Methanol → 5-tert-Butyl-7-(3,5-di-tert-butylphenyl)-6-methoxy-2-methyl-1H-indene

HRID 716469Notes

Reaction equation

HRID 716469 reaction equation
[C:1]([C:5]1[CH:13]=[C:12]2[C:8]([CH2:9][CH:10]([CH3:15])[C:11]2=O)=[C:7]([C:16]2[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:19]=[C:18]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:17]=2)[C:6]=1[O:30][CH3:31])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].CO.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C1(C)C=CC=CC=1>[C:1]([C:5]1[CH:13]=[C:12]2[C:8](=[C:7]([C:16]3[CH:21]=[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:19]=[C:18]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:17]=3)[C:6]=1[O:30][CH3:31])[CH2:9][C:10]([CH3:15])=[CH:11]2)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 6101p-Toluenesulfonic acidHCID 4311764Sodium borohydrideHCID 712309426-tert-Butyl-4-(3,5-di-tert-butylphenyl)-5-methoxy-2-methylindan-1-one

Product 1

HCID 712317445-tert-Butyl-7-(3,5-di-tert-butylphenyl)-6-methoxy-2-methyl-1H-indeneYield 100%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 16.3 g (38.8 mmol) of 6-tert-butyl-4-(3,5-di-tert-butylphenyl)-5-methoxy-2-methylindan-1-one in 200 ml of THF cooled to 5° C. 1.47 g (38.9 mmol) of NaBH4 was added. Further on, 80 ml of methanol was added dropwise to this mixture by vigorous stirring for ca. 7 h at 5° C. The resulting mixture was evaporated to dryness, and the residue was treated by 300 ml of dichloromethane and 300 ml of 2 M HCl. The organic layer was separated, the aqueous layer was additionally extracted with 100 ml of dichloromethane. The combined organic extract was evaporated to dryness to give a colorless oil. To a solution of this oil in 250 ml of toluene 0.1 g of TsOH was added, this mixture was refluxed with Dean-Stark head for 15 min and then cooled to room temperature using water bath. The resulting solution was washed by 10% aqueous Na2CO3. The organic layer was separated, the aqueous layer was extracted with 2×50 ml of dichloromethane. The combined organic extract was dried over K2CO3 and then passed through a short layer of silica gel 60 (40-63 um). The silica gel layer was additionally washed by 100 ml of dichloromethane. The combined organic elute was evaporated to dryness to give 15.7 g (99%) of a white crystalline product which was further used without an additional purification.

Workup

  1. customThe resulting mixture was evaporated to dryness
  2. additionthe residue was treated by 300 ml of dichloromethane and 300 ml of 2 M HCl
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was additionally extracted with 100 ml of dichloromethane
  5. extractionThe combined organic extract
  6. customwas evaporated to dryness
  7. customto give a colorless oil
  8. temperaturethis mixture was refluxed with Dean-Stark head for 15 min
  9. temperaturecooled to room temperature
  10. washThe resulting solution was washed by 10% aqueous Na2CO3
  11. customThe organic layer was separated
  12. extractionthe aqueous layer was extracted with 2×50 ml of dichloromethane
  13. extractionThe combined organic extract
  14. dry with materialwas dried over K2CO3
  15. washThe silica gel layer was additionally washed by 100 ml of dichloromethane
  16. washThe combined organic elute
  17. customwas evaporated to dryness

Sources & evidence

ORD record
ord-b94860964c164ed2bcd6331945e6c29c
Source dataset
uspto-grants-2015_11
Patent number
US09187583B2

Reaction notes

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