Hydrochloric Acid → HCID 59025495, compound

HRID 1444830Notes

Reaction equation

HRID 1444830 reaction equation
[C:1]1([O:9][CH3:10])[C:2](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O:3][CH3:4].C([Li])CCC.[Cl:16][C:17]1[CH:25]=[C:24]2[C:20]([CH2:21][CH2:22][C:23]2=O)=[CH:19][CH:18]=1.Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[Cl:16][C:17]1[CH:25]=[C:24]2[C:20](=[CH:19][CH:18]=1)[CH2:21][CH:22]=[C:23]2[C:8]1[CH:7]=[CH:6][CH:5]=[C:2]([O:3][CH3:4])[C:1]=1[O:9][CH3:10]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7043VeratroleHCID 521998p-Toluenesulfonic acid monohydrateHCID 51007056-Chloro-1-indanoneHCID 178418339Butyllithium

Product 1

HCID 59025495HCID 59025495, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Under an argon atmosphere, 45.9 ml of veratrole (49.78 g, 360.1 mol) are dissolved in 240 ml of THF and, at −78° C., 236.2 ml of a 1.6 M solution of n-butyllithium in THF (377.7 mol) are added drop wise. The reaction mixture is warmed to 0° C. and stirred at this temperature for 3 h. The mixture is cooled to −60° C., and 30.0 g of the compound from Example 16A (180.1 mol) dissolved in 150 ml of THF are added drop wise. The reaction mixture is warmed to room temperature over the course of 3 h and then acidified with 1 N hydrochloric acid and extracted with dichloromethane. The combined organic phases are dried over magnesium sulphate, and the solvent is removed in a rotary evaporator. The residue is is purified by filtration through silica gel (mobile phase: cyclohexane/ethyl acetate 5:1). The crude product [6-chloro-1-(2,3-dimethoxyphenyl)indan-1-ol] is dissolved in 1 l of dichloromethane and, after addition of 75 mg of 4-toluenesulphonic acid monohydrate (0.39 mol), stirred at RT for. 16 h. The reaction solution is washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution, dried over sodium sulphate and concentrated in a rotary evaporator. The residue is purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1). 10.5 g (20% of theory) of the title compound are obtained.

Workup

  1. temperatureThe mixture is cooled to −60° C.
  2. additionare added drop wise
  3. temperatureThe reaction mixture is warmed to room temperature over the course of 3 h
  4. extractionextracted with dichloromethane
  5. dry with materialThe combined organic phases are dried over magnesium sulphate
  6. customthe solvent is removed in a rotary evaporator
  7. filtrationThe residue is is purified by filtration through silica gel (mobile phase: cyclohexane/ethyl acetate 5:1)
  8. dissolutionThe crude product [6-chloro-1-(2,3-dimethoxyphenyl)indan-1-ol] is dissolved in 1 l of dichloromethane
  9. stirringstirred at RT for
  10. custom16 h
  11. washThe reaction solution is washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution
  12. dry with materialdried over sodium sulphate
  13. concentrationconcentrated in a rotary evaporator
  14. customThe residue is purified by chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1)

Sources & evidence

ORD record
ord-3f135d5f847c41e58e660bd7142e167b
Source dataset
uspto-grants-2010_02
Patent number
US07662956B2

Reaction notes

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