Diisopropylamine → HCID 19434960, compound

HRID 1736177Notes

Reaction equation

HRID 1736177 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([NH:16][C:17]1[CH:44]=[CH:43][C:20]([C:21]([O:23][C:24]2[C:29]([F:30])=[C:28]([F:31])[C:27]([F:32])=[C:26]([NH:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36])[C:25]=2[C:40](=[O:42])[CH3:41])=O)=[CH:19][C:18]=1[F:45])(=[O:15])[CH3:14].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[C:13]([NH:16][C:17]1[CH:44]=[CH:43][C:20]([C:21]2[O:23][C:24]3[C:29]([F:30])=[C:28]([F:31])[C:27]([F:32])=[C:26]([NH:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:36])[CH3:37])[C:25]=3[C:40](=[O:42])[CH:41]=2)=[CH:19][C:18]=1[F:45])(=[O:15])[CH3:14]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 19434884HCID 19434884, compoundHCID 178418339Butyllithium

Product 1

HCID 19434960HCID 19434960, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

0.83 mL (5.9 mmol) of diisopropylamine was dissolved in 10 mL of tetrahydrofuran under argon atmosphere, 3.5 mL of a 1.6 M solution of n-butyl lithium in n-hexane was added dropwise under ice-cooling and the solution was cooled to -78 ° C. To this solution was added a solution of 838 mg (1.79 mmol) of the above 2-acetyl-4,5,6-trifluoro-3-pivaloylaminophenyl 4-acetylamino-3-fluorobenzoate in 20 mL of tetrahydrofuran was added dropwise and the mixture was stirred for 2 hours while the temperature of the mixture was gradually raised to 0° C. An aqueous solution of ammonium chloride was added to the reaction solution, the mixture was extracted twice with ethyl acetate, the organic layer was washed once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilied off under reduced pressure, the residue was dissolved in 24 mL of ethanol, 6 mL of concentrated hydrochloric acid was added and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction solution and the precipitated crystals were collected by filtration to give 330 mg of 2-(4-acetylamino-3-fluorophenyl)-6,7,8-trifluoro-5-pivaloylamino-4H-1-benzopyran-4-one (yield: 77%).

Workup

  1. temperaturecooling
  2. additionwas added dropwise
  3. temperaturewas gradually raised to 0° C
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. washthe organic layer was washed once with an aqueous saturated solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. dissolutionthe residue was dissolved in 24 mL of ethanol
  8. addition6 mL of concentrated hydrochloric acid was added
  9. stirringthe mixture was stirred at room temperature for 4 hours
  10. additionWater was added to the reaction solution
  11. filtrationthe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-22082e35ae0f4b0b892abec116d827a9
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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