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

HRID 716442Notes

Reaction equation

HRID 716442 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 98,921.797%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 45.9 g (0.149 mmol) of 6-tert-butyl-5-methoxy-2-methyl-4-phenylindan-1-one in 300 ml of THF cooled to 5° C. 8.51 g (0.225 mol) of NaBH4 was added. Further on, 150 ml of methanol was added dropwise to this mixture by vigorous stirring for ca. 7 h at 5° C. The resulting mixture was stirred overnight at room temperature, and then 1 liter of cold water and 12 M HCl to pH˜1 were added. The crude product was extracted with 3×200 ml of dichloromethane, the combined organic extract was dried over K2CO3 and then evaporated to dryness. To a solution of the residue in 800 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 10% aqueous Na2CO3, 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). The silica gel layer was additionally washed by 100 ml of dichloromethane. The combined organic elute was evaporated to dryness. This procedure gave 43.1 g (99%) of yellowish oil which was further used without an additional purification.

Workup

  1. stirringThe resulting mixture was stirred overnight at room temperature
  2. extractionThe crude product was extracted with 3×200 ml of dichloromethane
  3. extractionthe combined organic extract
  4. dry with materialwas dried over K2CO3
  5. customevaporated to dryness
  6. additionTo a solution of the residue in 800 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 10% aqueous Na2CO3
  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 100 ml of dichloromethane
  14. washThe combined organic elute
  15. customwas evaporated to dryness

Sources & evidence

ORD record
ord-afef6bfea6b5497480ef6cba0b4c1562
Source dataset
uspto-grants-2015_11
Patent number
US09187583B2

Reaction notes

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