Ammonium Chloride → HCID 58830637, compound

HRID 2353390Notes

Reaction equation

HRID 2353390 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([Br:9])=[CH:4][C:3]=1[F:10].[Cl:11][C:12]1[N:17]=[CH:16][C:15]([C:18](N(C)OC)=[O:19])=[CH:14][CH:13]=1.[Cl-].[NH4+]>C1COCC1.[Li]CCCC.CCCCCC>[Br:9][C:5]1[C:6]([F:8])=[CH:7][C:2]([C:18]([C:15]2[CH:16]=[N:17][C:12]([Cl:11])=[CH:13][CH:14]=2)=[O:19])=[C:3]([F:10])[CH:4]=1

Participants

7

Reactant 3

HCID 25517Ammonium ChlorideHCID 675961,4-Dibromo-2,5-difluorobenzeneHCID 114355976-Chloro-N-methoxy-N-methylnicotinamide

Product 1

HCID 58830637HCID 58830637, compoundYield 35.9%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 178418339ButyllithiumSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of 1,4-dibromo-2,5-difluorobenzene (1.36 g) in anhydrous THF (20 ml) and 1.6M n-BuLi in hexane (3.43 ml) was stirred at −78° C. under nitrogen for 20 min. The reaction mixture was added to 6-chloro-N-methyl-N-(methyloxy)-3-pyridinecarboxamide (0.921 g) in THF (20 ml) and stirred at −78° C. The mixture was then stirred at −70° C. for 30 min allowed to warm to room temperature then cooled again to −70° C. and treated with 10% aqueous ammonium chloride. The reaction mixture was warmed to room temperature and partitioned between ethyl acetate and 10% aqueous ammonium chloride. The organic layer was separated using a hydrophobic filter tube and the solvent was removed under vacuum. The residue was purified using a silica SPE cartridge eluting with petroleum ether/ethyl acetate (9:1 to 1:3) to give impure title compound (0.548 g).

Workup

  1. stirringstirred at −78° C
  2. stirringThe mixture was then stirred at −70° C. for 30 min
  3. temperatureto warm to room temperature
  4. temperaturethen cooled again to −70° C.
  5. temperatureThe reaction mixture was warmed to room temperature
  6. custompartitioned between ethyl acetate and 10% aqueous ammonium chloride
  7. customThe organic layer was separated
  8. customthe solvent was removed under vacuum
  9. customThe residue was purified
  10. washeluting with petroleum ether/ethyl acetate (9:1 to 1:3)

Sources & evidence

ORD record
ord-eeea6de011b64302aaa689e8b16f04fe
Source dataset
uspto-grants-2010_07
Patent number
US07750026B2

Reaction notes

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