Water → HCID 54393038, compound

HRID 846603Notes

Reaction equation

HRID 846603 reaction equation
[H-].[Na+].C[O:4][C:5](=[O:15])[C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([NH2:13])=[CH:8][C:7]=1[OH:14].[CH2:16](Br)[CH:17]=[CH2:18].O>CN(C)C=O>[NH2:13][C:9]1[C:10]([Cl:12])=[CH:11][C:6]([C:5]([OH:4])=[O:15])=[C:7]([O:14][CH:16]=[CH:17][CH3:18])[CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 14883223Methyl 4-amino-5-chloro-2-hydroxybenzoate

Product 1

HCID 54393038HCID 54393038, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 60% sodium hydride/oil dispersion (1.52 g, 0.038 mole) in anhydrous dimethylformamide (50 ml) under nitrogen was treated in portions with 4-amino-5-chloro-2-hydroxybenzoic acid methyl ester (6.05 g, 0.030 mole), stirred at room temperature for 30 minutes, and treated with allyl bromide (4.60 g, 0.038 mole). The mixture was stirred at 95°±5° C. for one hour, cooled to room temperature, and added to water (250 ml). The solid was removed by filtration and saved, and the filtrate was extracted with ether (2×100 ml). The concentrated ethereal extracts were combined with the filtered solid, taken up in 20% aqueous ethanol (100 ml), treated with potassium hydroxide (10 g), and refluxed for 45 minutes. The ethanol was removed in vacuo and the aqueous solution was extracted with ether (50 ml) and petroleum ether (30°-60°, 50 ml), cooled (0° C.), and acidified to pH 4 with concentrated hydrochloric acid (17 ml). The suspension was filtered and solid was air dried, dissolved in methylene chloride (150 ml) containing a little methanol, dried (sodium sulfate), and concentrated in vacuo. Trituration from cold ether/petroleum ethers (30°-60°) and recrystallization from ethyl acetate/hexane (2 crops) afforded 4.25 g (62.2%) of the title compound as a pale tan solid; mp 136°-137° C.

Workup

  1. stirringThe mixture was stirred at 95°±5° C. for one hour
  2. temperaturecooled to room temperature
  3. customThe solid was removed by filtration
  4. extractionthe filtrate was extracted with ether (2×100 ml)
  5. additiontreated with potassium hydroxide (10 g)
  6. temperaturerefluxed for 45 minutes
  7. customThe ethanol was removed in vacuo
  8. extractionthe aqueous solution was extracted with ether (50 ml) and petroleum ether (30°-60°, 50 ml)
  9. temperaturecooled (0° C.)
  10. filtrationThe suspension was filtered
  11. customdried
  12. dissolutiondissolved in methylene chloride (150 ml)
  13. additioncontaining a little methanol
  14. dry with materialdried (sodium sulfate)
  15. concentrationconcentrated in vacuo
  16. customTrituration from cold ether/petroleum ethers (30°-60°) and recrystallization from ethyl acetate/hexane (2 crops)

Sources & evidence

ORD record
ord-b47a67045d0148d0b4a85d33c386484d
Source dataset
uspto-grants-1992_08
Patent number
US05137895

Reaction notes

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