Sulfuric Acid → HCID 17989294, compound

HRID 1444491Notes

Reaction equation

HRID 1444491 reaction equation
[C-]#N.[K+].[F:4][C:5]([F:17])([F:16])[C:6](=[O:15])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.S(=O)(=O)(O)O.[C:23](=O)(O)[O-:24].[Na+].CC(C[AlH]CC(C)C)C>O.C1(C)C=CC=CC=1.C1COCC1>[OH:15][C:6]([C:5]([F:16])([F:17])[F:4])([CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[CH:23]=[O:24]

Participants

9

Reactant 5

HCID 1118Sulfuric AcidHCID 9032Potassium CyanideHCID 14487Diisobutylaluminum hydrideHCID 1357671,1,1-Trifluoro-4-phenylbutan-2-oneHCID 516892Sodium Bicarbonate

Product 1

HCID 17989294HCID 17989294, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

200 mg (3.1 mmol) of potassium cyanide in 2 ml of water is added to 0.55 g (2.7 mmol) of 1,1,1-trifluoro-4-phenyl-butan-2-one (D. Yang; M -K. Wong; Z. Yan J. Org. Chem. (2000); 65; 4179-4184) in 4 mil of THF and 2 ml of water. It is cooled to 0° C., and 1 ml of a 25% sulfuric acid is added, allowed to heat to room temperature and stirred for 16 hours. Saturated sodium bicarbonate solution is added and extracted with ethyl acetate. After washing with saturated sodium chloride solution and drying on sodium sulfate, the crude cyanide, which is dissolved in 15 ml of diethyl ether and cooled to −70° C., is obtained quantitatively. 4.6 ml (5.5 mmol) of a 1.2 M DIBAL solution in toluene is added in drops over 10 minutes. It is allowed to heat for 2 hours to room temperature, quenched with 10% tartaric acid solution, and vigorous stirring is continued. After extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid are added. It is stirred vigorously for 12 hours and filtered through Celite. The phases are separated, and it is extracted again with ethyl acetate. After chromatography on silica gel (hexane/ethyl acetate 30%), 300 mg of still contaminated 2-hydroxy-4-phenyl-2-(trifluoromethyl)-butanal is obtained. 0.5 ml (2.4 mmol) of titanium tetraethylate is added to the thus obtained aldehyde and 200 mg (1.13 mmol) of 5-amino-8-fluoro-2-methylquinazoline in 15 ml of toluene, and the mixture is heated for 2 hours to 100° C. After the cooling, it is poured into water, and vigorous stirring is continued. The suspension is filtered through Celite and thoroughly rewashed with ethyl acetate. The phases of the filtrate are separated, and it is extracted again with ethyl acetate. It is dried on sodium sulfate, and the solvent is removed in a vacuum. After chromatography on silica gel (hexane/ethyl acetate 30%), 100 mg of 1-(8-fluoro-2-methylquinazolin-5-ylimino)-4-phenyl-2-(trifluoromethyl)butan-2-ol is obtained. The imine is taken up in 5 ml of dichloromethane and cooled to −70° C. 1 ml (1 mmol) of a 1 M titanium tetrachloride solution in dichloromethane is added in drops over 10 minutes and stirred for one hour. The solution is poured into saturated sodium bicarbonate solution and stirred vigorously for 15 minutes. It is extracted with ethyl acetate, washed with. saturated sodium chloride solution, and dried on sodium sulfate. After concentration by evaporation and chromatography-on silica gel (hexane/ethyl acetate 50%), 44 mg of the desired product is obtained.

Workup

  1. temperatureto heat to room temperature
  2. extractionextracted with ethyl acetate
  3. washAfter washing with saturated sodium chloride solution
  4. customdrying on sodium sulfate
  5. dissolutionthe crude cyanide, which is dissolved in 15 ml of diethyl ether
  6. temperaturecooled to −70° C.
  7. customis obtained quantitatively
  8. temperatureto heat for 2 hours to room temperature
  9. customquenched with 10% tartaric acid solution
  10. stirringvigorous stirring
  11. extractionAfter extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid
  12. additionare added
  13. stirringIt is stirred vigorously for 12 hours
  14. filtrationfiltered through Celite
  15. customThe phases are separated
  16. extractionit is extracted again with ethyl acetate

Sources & evidence

ORD record
ord-212922d7fa1a47b9ae1c40367a77ad90
Source dataset
uspto-grants-2010_02
Patent number
US07662821B2

Reaction notes

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