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

HRID 1626374Notes

Reaction equation

HRID 1626374 reaction equation
Cl[CH2:2][CH2:3][C:4]([C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([OH:13])=[CH:8][C:7]=1[OH:14])=[O:5].[OH-].[Na+].Cl>O>[Cl:12][C:10]1[CH:11]=[C:6]2[C:7](=[CH:8][C:9]=1[OH:13])[O:14][CH2:2][CH2:3][C:4]2=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67166662HCID 67166662, compound

Product 1

HCID 203471666-Chloro-7-hydroxy-2,3-dihydro-4H-1-benzopyran-4-oneYield 62.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
10 °C

Procedure

A 20-liter 4-neck round-bottom flask was charged with water (10 L) and 3-chloro-1-(5-chloro-2,4-dihydroxyphenyl)propan-1-one (1.62 kg, 6.89 mol), and the resulting mixture was stirred and cooled to 10° C. A solution of sodium hydroxide (606.5 g, 15.16 mol) in water (2.96 L) was added dropwise over 40-60 minutes, maintaining the temperature at 10-15° C. The resulting mixture was stirred at ambient temperature for a further 30 minutes, then cooled to 5° C. Concentrated hydrochloric acid (1.31 L, 15.98 mol) was added dropwise over 30 minutes, maintaining the temperature at or below 10° C. The resulting mixture was stirred at ambient temperature for a further 30 minutes, and the resulting precipitate was collected by filtration, washed with water (3×5.5 L), and dried at 40° C. until the moisture content fell below 1%. This crude product (1.2 kg) was transferred to a 10-liter 4-neck round-bottom flask and stirred with acetonitrile (6.0 L) at ambient temperature for 2 hours, then cooled to 0-5° C. and stirred for an additional 2 hours. The resulting precipitate was collected by filtration, washed with 4:1 water:acetonitrile (1.5 L) and water (1.2 L), and dried in a fan dryer at 40° C. until the moisture content fell below 0.5%, to afford 6-chloro-7-hydroxychroman-4-one as an off-white solid (858 g, 62.7% yield).

Workup

  1. temperaturemaintaining the temperature at 10-15° C
  2. stirringThe resulting mixture was stirred at ambient temperature for a further 30 minutes
  3. temperaturecooled to 5° C
  4. temperaturemaintaining the temperature at or below 10° C
  5. stirringThe resulting mixture was stirred at ambient temperature for a further 30 minutes
  6. filtrationthe resulting precipitate was collected by filtration
  7. washwashed with water (3×5.5 L)
  8. customdried at 40° C. until the moisture content
  9. customThis crude product (1.2 kg) was transferred to a 10-liter 4-neck round-bottom flask
  10. stirringstirred with acetonitrile (6.0 L) at ambient temperature for 2 hours
  11. temperaturecooled to 0-5° C.
  12. stirringstirred for an additional 2 hours
  13. filtrationThe resulting precipitate was collected by filtration
  14. washwashed with 4:1 water
  15. dry with materialacetonitrile (1.5 L) and water (1.2 L), and dried in a fan dryer at 40° C. until the moisture content

Sources & evidence

ORD record
ord-c0750d6e0f8f43dca058a6d635bf0e3c
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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