Hydrochloric Acid → 5-tert-butyl-6-methoxy-2-methyl-7-phenyl-1H-indene

HRID 716443Notes

Reaction equation

HRID 716443 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][CH:19]=[CH:18][CH:17]=2)[C:6]=1[O:22][CH3:23])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].CO.Cl>C1COCC1.O>[C:1]([C:5]1[CH:13]=[C:12]2[C:8](=[C:7]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6]=1[O:22][CH3:23])[CH2:9][C:10]([CH3:15])=[CH:11]2)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 4311764Sodium borohydrideHCID 712309196-tert-Butyl-5-methoxy-2-methyl-4-phenylindan-1-one

Product 1

HCID 602106945-tert-butyl-6-methoxy-2-methyl-7-phenyl-1H-indeneYield 99,744.203%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 44.3 g (0.144 mmol) of 6-tert-butyl-5-methoxy-2-methyl-4-phenylindan-1-one in 150 ml of THF cooled to 5° C. 2.72 g (71.9 mmol) of NaBH4 was added. Further on, 75 ml of methanol was added dropwise to this mixture by vigorous stirring for 1 h at 5° C. The resulting mixture was stirred additionally 1 h at 5° C., then 0.5 h at room temperature, and then added to 1 liter of cold water and 30 ml of 12 M HCl in separating funnel. The crude product was extracted consequentially with 250, 100 and 50 ml of dichloromethane, and the combined organic extract was evaporated to dryness. To a solution of the residue in 500 ml of toluene 1.0 g of TsOH was added, this mixture was refluxed with Dean-Stark head for 10 min and then cooled to room temperature using water bath. The resulting solution was washed by aqueous K2CO3 (20 g K2CO3 in 200 ml of H2O), the organic layer was separated, the aqueous layer was extracted with 2×50 ml of dichloromethane. The combined organic solution was dried over K2CO3 and then passed through short layer of silica gel 60 (40-63 um, ca. 10 g). The silica gel layer was additionally washed by 50 ml of dichloromethane. The combined organic elute was evaporated to dryness. This procedure gave 42.0 g (˜100%) of yellowish oil which was further used without an additional purification.

Workup

  1. stirringThe resulting mixture was stirred additionally 1 h at 5° C.
  2. customin separating funnel
  3. extractionThe crude product was extracted consequentially with 250, 100 and 50 ml of dichloromethane
  4. extractionthe combined organic extract
  5. customwas evaporated to dryness
  6. additionTo a solution of the residue in 500 ml of toluene 1.0 g of TsOH was added
  7. temperaturethis mixture was refluxed with Dean-Stark head for 10 min
  8. temperaturecooled to room temperature
  9. washThe resulting solution was washed by aqueous K2CO3 (20 g K2CO3 in 200 ml of H2O)
  10. customthe organic layer was separated
  11. extractionthe aqueous layer was extracted with 2×50 ml of dichloromethane
  12. dry with materialThe combined organic solution was dried over K2CO3
  13. washThe silica gel layer was additionally washed by 50 ml of dichloromethane
  14. washThe combined organic elute
  15. customwas evaporated to dryness

Sources & evidence

ORD record
ord-68f3d05b2229430f92d89f51f1c27ec5
Source dataset
uspto-grants-2015_11
Patent number
US09187583B2

Reaction notes

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