Methanol → 5-t-Butyl-6-methoxy-2-methyl-7-(4-t-butylphenyl)-1h-indene

HRID 716465Notes

Reaction equation

HRID 716465 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]=[CH:20][C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=2)[C:6]=1[O:26][CH3:27])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].CO.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C1(C)C=CC=CC=1.CCCCCC>[C:1]([C:5]1[CH:13]=[C:12]2[C:8](=[C:7]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:18][CH:17]=3)[C:6]=1[O:26][CH3:27])[CH2:9][C:10]([CH3:15])=[CH:11]2)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 887MethanolHCID 6101p-Toluenesulfonic acidHCID 4311764Sodium borohydrideHCID 712308126-tert-Butyl-4-(4-tert-butylphenyl)-5-methoxy-2-methylindan-1-one

Product 1

HCID 712310325-t-Butyl-6-methoxy-2-methyl-7-(4-t-butylphenyl)-1h-indeneYield 86.2%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 28.9 g (79.2 mmol) of 6-tert-butyl-4-(4-tert-butylphenyl)-5-methoxy-2-methylindan-1-one in 400 ml of THF cooled to 5° C. 5.00 g (132 mmol) of NaBH4 was added. Further on, 100 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 wad partitioned between 500 ml of dichloromethane and 1000 ml of 0.5 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 500 ml of toluene 1.0 g of TsOH was added. The formed mixture was refluxed with Dean-Stark head for 15 min and then cooled to room temperature using water bath. The resulting reddish solution was washed by 10% aqueous Na2CO3, the organic layer was separated, the aqueous layer was extracted with 2×100 ml of dichloromethane. The combined organic extract was dried over K2CO3 and then passed through short pad of silica gel 60 (40-63 um). The silica gel pad was additionally washed by 50 ml of dichloromethane. The combined organic elute was evaporated to dryness to give a yellowish crystalline mass. The product was isolated by re-crystallization of this mass from 150 ml of hot n-hexane. Crystals precipitated at 5° C. were collected dried in vacuum. This procedure gave 23.8 g of white macrocrystalline 5-tert-butyl-7-(4-tert-butylphenyl)-6-methoxy-2-methyl-1H-indene. The mother liquor was evaporated to dryness and the residue was recrystallized from 20 ml of hot n-hexane in the same way. This procedure gave additional 2.28 g of the product. Thus, the total yield of the title product was 26.1 g (95%).

Workup

  1. customThe resulting mixture was evaporated to dryness
  2. customthe residue wad partitioned between 500 ml of dichloromethane and 1000 ml of 0.5 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. temperatureThe formed mixture was refluxed with Dean-Stark head for 15 min
  9. temperaturecooled to room temperature
  10. washThe resulting reddish solution was washed by 10% aqueous Na2CO3
  11. customthe organic layer was separated
  12. extractionthe aqueous layer was extracted with 2×100 ml of dichloromethane
  13. extractionThe combined organic extract
  14. dry with materialwas dried over K2CO3
  15. washThe silica gel pad was additionally washed by 50 ml of dichloromethane
  16. washThe combined organic elute
  17. customwas evaporated to dryness
  18. customto give a yellowish crystalline mass
  19. customCrystals precipitated at 5° C.
  20. customwere collected
  21. customdried in vacuum

Sources & evidence

ORD record
ord-a159ac21d433407991d2aaa533a39da8
Source dataset
uspto-grants-2015_11
Patent number
US09187583B2

Reaction notes

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