Hydrochloric Acid → 6-Chloro-7-hydroxy-2,3-dihydro-4H-1-benzopyran-4-one

HRID 1047970Notes

Reaction equation

HRID 1047970 reaction equation
FC(F)(F)S(O)(=O)=O.[Cl:9][C:10]1[CH:16]=[CH:15][C:13]([OH:14])=[CH:12][C:11]=1[OH:17].Cl[CH2:19][CH2:20][C:21](O)=[O:22].[OH-].[Na+].Cl>>[Cl:9][C:10]1[CH:16]=[C:15]2[C:13](=[CH:12][C:11]=1[OH:17])[O:14][CH2:19][CH2:20][C:21]2=[O:22]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 17314-ChlororesorcinolHCID 78993-Chloropropionic acidHCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acid

Product 1

HCID 203471666-Chloro-7-hydroxy-2,3-dihydro-4H-1-benzopyran-4-oneYield 208.7%

Conditions

Temperature
50 °C

Procedure

A 50-liter reactor was charged with trifluoromethanesulfonic acid (8 kg) and the reactor cooled in an ice bath. To the reactor was added 4-chlororesorcinol (1.6 kg, 11.1 mol), in portions, at a rate such that the internal temperature did not exceed 10° C. To the reactor was then added 3-chloropropanoic acid (1.26 kg, 11.6 mol), and the resulting mixture was warmed to ambient temperature, then heated at 45-55° C. for 6 hours. The reaction mixture was then slowly added to ice-water (20 L). The resulting slurry was stirred for 2 hours, and the resulting precipitate was collected by filtration, washed with water (12 L), and air-dried. This material was added to a solution of sodium hydroxide (1.1 kg, 27.5 mol) in ice-water (24 L), at a rate such that the internal temperature did not exceed 20° C. The resulting solution was stirred below 20° C. for 1 hour, then cooled, and treated with concentrated hydrochloric acid (2.5 L), at a rate such that the temperature did not exceed 10° C. The resulting slurry was stirred below 10° C. for 1 hour, and the resulting precipitate was collected by filtration, washed with water (10 L), and partially air-dried. The crude solids from four such procedures were combined and added to a mixture of acetone (32 L) and water (40 L), and the resulting mixture was stirred and heated until a clear solution formed. This solution was then cooled to 5-10° C., and the resulting precipitate was collected by filtration, washed with water (12 L), and dried to afford 6-chloro-7-hydroxychroman-4-one as a white solid (4.6 kg, 52% yield).

Workup

  1. temperaturethe reactor cooled in an ice bath
  2. customdid not exceed 10° C
  3. filtrationthe resulting precipitate was collected by filtration
  4. washwashed with water (12 L)
  5. customair-dried
  6. customdid not exceed 20° C
  7. stirringThe resulting solution was stirred below 20° C. for 1 hour
  8. temperaturecooled
  9. customdid not exceed 10° C
  10. stirringThe resulting slurry was stirred below 10° C. for 1 hour
  11. filtrationthe resulting precipitate was collected by filtration
  12. washwashed with water (10 L)
  13. custompartially air-dried
  14. additionadded to a mixture of acetone (32 L) and water (40 L)
  15. stirringthe resulting mixture was stirred
  16. temperatureheated until a clear solution
  17. customformed
  18. temperatureThis solution was then cooled to 5-10° C.
  19. filtrationthe resulting precipitate was collected by filtration
  20. washwashed with water (12 L)
  21. customdried

Sources & evidence

ORD record
ord-07e67995b50245d4af4e496d3342eb0c
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

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