Hydrochloric Acid → HCID 21488671, compound

HRID 1580641Notes

Reaction equation

HRID 1580641 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 is added, with stirring, 320 ml. of an n-heptane solution of n-butyl lithium containing 1.0 mole of the latter. The addition is carried out during 50 minutes and is followed by stirring 2 hours more at -50° C. The cold solution is 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 is stirred under a nitrogen atmosphere for 20 hours, at which time 1000 ml. of 2N hydrochloric acid is added. The aqueous layer is separated and discarded. The organic layer is filtered to remove suspended solid material and the filtrate is washed with cold, dilute aqueous sodium hydroxide solution. Three layers are 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, is concentrated to give 101 g. of a semi-solid which is then extracted with 2100 ml. of hot Skellysolve B hexanes. Evaporation of the extract gives 39.9 g. of crude product, m.p. 106°-116° C. Recrystallization of this material from Skellysolve B gives purified 2-acetamido-5-chloro-2',6'-difluorobenzophenone, m.p. 118°-120° c.

Workup

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

Sources & evidence

ORD record
ord-e74dfb6901ff4a6ba2164eaa7d9404d8
Source dataset
uspto-grants-1976_01
Patent number
US03933794

Reaction notes

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