6-Fluoro-4-chromanone hydantoin → 4-Amino-6-fluoro-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid

HRID 1583468Notes

Reaction equation

HRID 1583468 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:11]3([C:15](=[O:16])NC(=O)[NH:12]3)[CH2:10][CH2:9][O:8][C:5]2=[CH:6][CH:7]=1.[OH2:18].O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>O>[NH2:12][C:11]1([C:15]([OH:16])=[O:18])[C:4]2[C:5](=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[O:8][CH2:9][CH2:10]1

Participants

4

Reactant 2

HCID 52526-Fluoro-4-chromanone hydantoinHCID 17749109Barium hydroxide, octahydrate

Product 1

HCID 132985914-Amino-6-fluoro-3,4-dihydro-2H-1-benzopyran-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A stirred slurry of 78 g (0.33 mole) of (RS)-6-fluoro-spiro-[chroman-4,4'-imidazolidine]-2',5'-dione and 208.3 g (0.66 mole) of barium hydroxide octahydrate in 585 ml of water was slowly heated to reflux over 3 hours and refluxed 16 hours. The slurry was cooled to 80° C. and powdered NH4CO3 (78 g) added portionwise over 5 minutes. Moderate foaming was noted. After stirring 1.5 hours at 80° C., the mixture was cooled to 60° C., and filtered over diatomaceous earth with 2×100 ml hot water for wash. The combined filtrate and washes were stripped to 200 ml and allowed to stand overnight. 2-Propanol (600 ml) was added and the mixture heated to 70° C. to dissolve precipitated solids. The hot solution was treated with activated carbon, filtered over diatomaceous earth and washed with hot 1:1 water:2-propanol. The combined filtrate and washes were stripped to 200 ml, and water chased with 3×300 ml fresh 2-propanol. The resulting thick slurry was diluted with 200 ml additional 2-propanol, cooled to 5° C., granulated for 0.5 hour, filtered and air dried to yield title product, 63.5 g, 91.2%, mp 252°-253° C. (dec).

Workup

  1. temperatureto reflux over 3 hours
  2. temperaturerefluxed 16 hours
  3. temperaturethe mixture was cooled to 60° C.
  4. filtrationfiltered over diatomaceous earth with 2×100 ml hot water
  5. washfor wash
  6. waitto stand overnight
  7. addition2-Propanol (600 ml) was added
  8. temperaturethe mixture heated to 70° C.
  9. dissolutionto dissolve
  10. customprecipitated solids
  11. additionThe hot solution was treated with activated carbon
  12. filtrationfiltered over diatomaceous earth
  13. washwashed with hot 1:1 water
  14. additionThe resulting thick slurry was diluted with 200 ml additional 2-propanol
  15. temperaturecooled to 5° C.
  16. waitgranulated for 0.5 hour
  17. filtrationfiltered
  18. customair dried

Sources & evidence

ORD record
ord-82b053e5a82b42198baffab00610af5b
Source dataset
uspto-grants-1985_11
Patent number
US04551542

Reaction notes

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