Methanol → HCID 13646817, compound

HRID 2118891Notes

Reaction equation

HRID 2118891 reaction equation
[Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][CH:7]([CH2:13][CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:8]2=[O:12])=[CH:4][C:3]=1[O:19][CH3:20].[H-].[Na+].[CH3:23]I.CO>C1(C)C=CC=CC=1.CN(C)C=O.C(O)(=O)C>[Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][C:7]([CH2:13][CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)([CH3:23])[C:8]2=[O:12])=[CH:4][C:3]=1[O:19][CH3:20]

Participants

8

Reactant 4

HCID 887MethanolHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 12395559HCID 12395559, compound

Product 1

HCID 13646817HCID 13646817, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Procedure

6,7-Dichloro-2-cyclopentylmethyl-2,3-dihydro -5-methoxy-1H-inden-1-one (56.7 g., 0.181 mole) dissolved in dry toluene (200 ml.) is added dropwise with stirring under nitrogen over 1 hour at room temperature to a suspension of sodium hydride (56% in mineral oil, 8.74 g. 0.204 mole) in toluene (50 ml) and dry dimethylformamide (220 ml.) The mixture is stirred at room temperature for 1.75 hours after completion of the addition, cooled to 0° C., and then methyl iodide (25 ml., 0.4 mole) is added at 0°-5° C. After stirring at 5° for 25 minutes and for one hour at room temperature, methanol (15 ml.) is slowly added followed by acetic acid (10 ml.). The mixture is poured into ice water (1500 ml.) the layers are separated and the aqueous phase extracted three times with toluene (150 ml.) and then with methylene chloride (150 ml.). The combined organic extracts are washed with water, dried over magnesium sulfate and concentrated under vacuum. The residue is triturated with a mixture of hexane and petroleum ether (1:1) are filtered. The solid (50 g.) is recrystallized from a mixture of methylcyclohexane (110 ml.) and hexane (55 ml.) to obtain 38 g. of product, m.p. 75°-77° C. The filtrates from the recrystallization are concentrated and the residue recrystallized from methylcyclohexane to obtain a second drop of 5.5 g. for a total yield of 73%.

Workup

  1. additionis added dropwise
  2. additionafter completion of the addition
  3. temperaturecooled to 0° C.
  4. stirringAfter stirring at 5° for 25 minutes and for one hour at room temperature
  5. customare separated
  6. extractionthe aqueous phase extracted three times with toluene (150 ml.)
  7. washThe combined organic extracts are washed with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe residue is triturated with a mixture of hexane and petroleum ether (1:1)
  11. filtrationare filtered
  12. customThe solid (50 g.) is recrystallized from a mixture of methylcyclohexane (110 ml.) and hexane (55 ml.)
  13. customto obtain 38 g
  14. customThe filtrates from the recrystallization
  15. concentrationare concentrated
  16. customthe residue recrystallized from methylcyclohexane
  17. customto obtain a second drop of 5.5 g

Sources & evidence

ORD record
ord-a22f6a7dc0d84d088ccb1188658a9bd4
Source dataset
uspto-grants-1987_07
Patent number
US04680414

Reaction notes

Loading…