Hydrochloric Acid → HCID 21488671, compound

HRID 1288045Notes

Reaction equation

HRID 1288045 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=1.C([Li])CCC.[Cl:14][C:15]1[CH:16]=[CH:17][C:18]2[N:23]=[C:22]([CH3:24])[O:21][C:20](=[O:25])[C:19]=2[CH:26]=1.Cl>O1CCCC1.C1C=CC=CC=1.CCCCCCC>[C:22]([NH:23][C:18]1[CH:17]=[CH:16][C:15]([Cl:14])=[CH:26][C:19]=1[C:20]([C:3]1[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=1[F:8])=[O:25])(=[O:21])[CH3:24]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 97411,3-DifluorobenzeneHCID 2911346-Chloro-2-methyl-4H-3,1-benzoxazin-4-oneHCID 178418339Butyllithium

Product 1

HCID 21488671HCID 21488671, compound

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolvent

Procedure

To a solution of 114 g. (1.0 mole) of m-difluorobenzene in 800 ml. of dry tetrahydrofuran cooled to -50° C. and maintained under a nitrogen atmosphere was added, with stirring, 320 ml. of an n-heptane solution of n-butyl lithium containing 1.0 mole of the latter. The addition was carried out during 50 minutes and was followed by stirring 2 hours more at -50° C. The cold solution was then added with stirring during 50 minutes to a solution of 187.8 g. (0.97 mole) of 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one [J. Am. Chem. Soc. 70, 2423 (1948)] in 1400 ml. of benzene and 1000 ml. of tetrahydrofuran at 25° C. The mixture was stirred under a nitrogen atmosphere for 20 hours, at which time 1000 ml. of 2N hydrochloric acid was added. The aqueous layer was separated and discarded. The organic layer was filtered to remove suspended solid material and the filtrate was washed with cold, dilute aqueous sodium hydroxide solution. Three layers were present, a light colored aqueous phase, a dark brown aqueous phase, and an organic phase. The organic phase, after being dried with anhydrous sodium sulfate, was concentrated to give 101 g. of a semi-solid which was then extracted with 2100 ml. of hot Skellysolve B hexanes. Evaporation of the extract gave 39.9 g. of crude product of melting point 106°-116° C. Recrystallization of this material from Skellysolve B gave purified 2-acetamido-5-chloro-2',6'-difluorobenzophenone of melting point 118°-120° C.

Workup

  1. temperaturemaintained under a nitrogen atmosphere
  2. additionwas added
  3. additionThe addition
  4. stirringby stirring 2 hours more at -50° C
  5. additionThe cold solution was then added
  6. stirringwith stirring during 50 minutes to a solution of 187.8 g
  7. customat 25° C
  8. stirringThe mixture was stirred under a nitrogen atmosphere for 20 hours, at which time 1000 ml
  9. customThe aqueous layer was separated
  10. filtrationThe organic layer was filtered
  11. customto remove
  12. washthe filtrate was washed with cold, dilute aqueous sodium hydroxide solution
  13. dry with materialThe organic phase, after being dried with anhydrous sodium sulfate
  14. concentrationwas concentrated
  15. customto give 101 g
  16. extractionof a semi-solid which was then extracted with 2100 ml
  17. customEvaporation of the extract
  18. customgave 39.9 g
  19. customRecrystallization of this material from Skellysolve B
  20. customgave
  21. custompurified 2-acetamido-5-chloro-2',6'-difluorobenzophenone of melting point 118°-120° C.

Sources & evidence

ORD record
ord-36eaf520d5f143ab8e83510cf7c41337
Source dataset
uspto-grants-1976_10
Patent number
US03987052

Reaction notes

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