Hydrochloric Acid → HCID 71231034, compound

HRID 716462Notes

Reaction equation

HRID 716462 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:14])[C:6]2=[O:13].[BH4-].[Na+].Cl.Br[C:19]1C=CC(OC)=C2C=1CC(C)C2O.[OH-].[K+].CI>C1COCC1.O.CS(C)=O.CO>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:14])[CH:6]2[O:13][CH3:19]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 4311764Sodium borohydrideHCID 707008274-Bromo-7-methoxy-2-methyl-2,3-dihydro-1H-inden-1-oneHCID 71230859HCID 71230859, compound

Product 1

HCID 71231034HCID 71231034, compound

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 104 g (0.407 mmol) of 4-bromo-7-methoxy-2-methylindan-1-one and 15.0 g (0.397 mmol) of NaBH4 in a mixture of 410 ml of THF 205 ml of methanol was added dropwise with vigorous stirring for 4 h at +5° C. This mixture was stirred overnight at room temperature and then added to 1 liter of cold water. The resulting mixture was carefully acidified by 2 M HCl to pH 5.0, and the formed indan-1-ol was extracted with 500 ml of dichloromethane. The aqueous layer was additionally extracted with 2×200 ml of dichloromethane. The combined organic extract was evaporated to dryness. To the resulting yellowish liquid of the crude 4-bromo-7-methoxy-2-methylindan-1-ol 800 ml of DMSO, 92.0 g (1.64 mol, 4.0 eq) of KOH, and 116 g (0.817 mol, 2.0 eq) of MeI were added. This mixture was stirred for 3 h at ambient temperature and then added to 3 L of cold water. The crude product was extracted with dichloromethane (500 ml, then 3×250 ml). The combined organic extract was washed 5 times by 1 liter of water and then evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 μm; eluent: hexanes-dichloromethane=2:1, then 1:2 and, finally, 1:5, vol.) followed by rectification in vacuum, 149-154° C./8 mm Hg. Yield 96.0 g (87%) of a ca. 1 to 2 mixture of two diastereomers.

Workup

  1. additionwas added dropwise
  2. stirringThis mixture was stirred overnight at room temperature
  3. extractionthe formed indan-1-ol was extracted with 500 ml of dichloromethane
  4. extractionThe aqueous layer was additionally extracted with 2×200 ml of dichloromethane
  5. extractionThe combined organic extract
  6. customwas evaporated to dryness
  7. stirringThis mixture was stirred for 3 h at ambient temperature
  8. extractionThe crude product was extracted with dichloromethane (500 ml
  9. extractionThe combined organic extract
  10. washwas washed 5 times by 1 liter of water
  11. customevaporated to dryness
  12. customThe product was isolated by flash chromatography on silica gel 60 (40-63 μm
  13. customfollowed by rectification in vacuum, 149-154° C./8 mm Hg
  14. additionYield 96.0 g (87%) of a ca. 1 to 2 mixture of two diastereomers

Sources & evidence

ORD record
ord-b94743055d6c486c83b8d679a86861ac
Source dataset
uspto-grants-2015_11
Patent number
US09187583B2

Reaction notes

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