Phosphoric Acid → 4-(2,5-Dimethoxy-3,4,6-trimethylphenyl)-4-phenylbutanol

HRID 1646817

Reaction equation

HRID 1646817 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[CH2:6]([C:13]1[C:18](C)=[C:17]([O:20]C)C(C)=C(C)C=1OC)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.BrCC[CH2:29][OH:30].O1CCCCC1O[CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][O:39]1.P(=O)(O)(O)O.[CH:49](OC(C)C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>O1CCCC1.CC(C)(N)C(C)(C)N.CCCCCC>[CH3:29][O:30][C:1]1[C:42]([CH3:43])=[C:41]([CH3:49])[C:40]([O:39][CH3:38])=[C:3]([CH3:4])[C:2]=1[CH:6]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[CH2:13][CH2:18][CH2:17][OH:20]

Participants

12

Reactant 8

HCID 1004Phosphoric AcidHCID 6101p-Toluenesulfonic acidHCID 7914Diisopropyl EtherHCID 123083-Bromo-1-propanolHCID 263182Tetrahydropyranyl etherHCID 516892Sodium BicarbonateHCID 190880201-Benzyl-2,5-dimethoxy-3,4,6-trimethylbenzeneHCID 178418339Butyllithium

Product 1

HCID 190880534-(2,5-Dimethoxy-3,4,6-trimethylphenyl)-4-phenylbutanolYield 82%

Reagents, catalysts & solvents 3

HCID 1233902,3-Butanediamione, 2,3-dimethyl-CatalystHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A 16.3 ml (26 mmole) of n-butyllithium.hexane solution was added dropwise to 7.02 g (26.0 mmole) of 1-benzyl-2,5-dimethoxy-3,4,6-trimethylbenzene and 4.32 ml (26×1.1 mmole) of 1,1,2,2-tetramethylethylenediamine dissolved in anhydrous tetrahydrofuran (70 ml), under an atmosphere of argon at 50° C. over the period of 10 minutes, followed by stirring at 50° to 56° C. for 20 minutes. Then, a solution of 5.80 g (26 mmole) of 3-bromopropanol.tetrahydropyranyl ether in tetrahydrofuran (30 ml) was added dropwise to the mixed solution over the period of 10 minutes, followed by stirring at 50° C. for further 10 minutes. After ice-cooling, a 10% aqueous phosphoric acid solution was added to make the solution acid, and isopropyl ether was added to conduct extraction. The organic layer was separated out, washed with aqueous saturated sodium chloride solution, dried (magnesium sulfate) and evaporated. The residue was dissolved in methanol (70 ml), and 0.25 g (26×1/20 mmole) of p-toluenesulfonic acid was added to the solution, followed by stirring at 70° C. for 15 minutes. After cooling by standing at room temperature, an aqueous sodium hydrogen-carbonate solution was added for neutralization, and the solvent was evaporated. Isopropyl ether and water were added to the residue to effect extraction, and the isopropyl ether layer was washed with aqueous sodium chloride solution, dried (magnesium sulfate) and evaporated. The residual solution was chromatographed on a silica gel column to effect purification (elution with isopropyl ether) to thereby give 7.00 g (82%) of 4-(2,5-dimethoxy-3,4,6-trimethylphenyl)-4-phenylbutanol. Its typical physical properties and nuclear magnetic resonance spectrum data are shown in Table 14.

Workup

  1. stirringby stirring at 50° C. for further 10 minutes
  2. temperatureAfter ice-cooling
  3. additionwas added
  4. extractionextraction
  5. customThe organic layer was separated out
  6. washwashed with aqueous saturated sodium chloride solution
  7. dry with materialdried (magnesium sulfate)
  8. customevaporated
  9. dissolutionThe residue was dissolved in methanol (70 ml)
  10. stirringby stirring at 70° C. for 15 minutes
  11. temperatureAfter cooling
  12. customby standing at room temperature
  13. customthe solvent was evaporated
  14. additionIsopropyl ether and water were added to the residue to effect extraction
  15. washthe isopropyl ether layer was washed with aqueous sodium chloride solution
  16. dry with materialdried (magnesium sulfate)
  17. customevaporated
  18. customThe residual solution was chromatographed on a silica gel column to effect purification (elution with isopropyl ether)

Sources & evidence

ORD record
ord-d4115488ff214cc1b4c3e82522f03e35
Source dataset
uspto-grants-1993_01
Patent number
US05180742

Linked notes

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