Acetic Acid → HCID 87621994, compound

HRID 1191613Notes

Reaction equation

HRID 1191613 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:12])[NH:7]2.[F:13][C:14]([F:23])([F:22])[C:15]([OH:21])([CH2:18][O:19][CH3:20])[CH:16]=O.[C:24](O)(=O)[CH3:25].[F-].[NH4+]>C1(C)C=CC=CC=1.O1CCOCC1.CCCCO.CCCCO.CCCCO.CCCCO.[Ti].C(OCC)(=O)C>[F:13][C:14]([F:23])([F:22])[C:15]([OH:21])([CH2:18][O:19][CH3:20])[C:16](=[N:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:12])[NH:7]2)[C:25]1[CH:24]=[CH:4][CH:3]=[CH:2][CH:11]=1

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 25516Ammonium fluorideHCID 157190785-Amino-1,2-dihydroquinolin-2-oneHCID 87564755HCID 87564755, compound

Product 1

HCID 87621994HCID 87621994, compound

Reagents, catalysts & solvents 4

HCID 521701TetrabutoxytitaniumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To 194 mg (1.2 mmol) 5-amino-1H-quinolin-2-one and 300 mg (1.2 mmol) 3,3,3-trifluoro-2-hydroxy-2-methoxymethypropan-1-one in 4 ml toluene and 1 ml 1,4-dioxane are added 0.26 ml acetic acid and 1 ml tetrabutyl orthotitanate. The mixture is heated over 20 hours to 110° C., cooled to room temperature and poured into aqueous ammonium fluoride solution. Ethyl acetate is added and the mixture is stirred vigorously for 30 minutes. Phases are separated and two times extracted with ethylacetate. The combined organic phases are concentrated to yield quantitatively 5-[(3,3,3-trifluoro-2-hydroxy-2-methoxymethyl-1-phenylpropylidene)amino]-1H-quinolin-2-one. 396 mg (1 mmol) imine in 22 ml methanol is cooled to 5° C. and 700 mg sodium boron hydride are added in multiple portions over the period of 24 hours. The reaction is quenched by addition of saturated ammonium chloride solution and diluted with water and ethyl acetate. The phases are separated, the aqueous layer is extracted with ethyl acetate, the combined organic phases are washed with brine and dried over sodium sulphate. After removal of the solvent flash chromatography on silica gel (ethyl acetate in hexane 0 to 80%) yields 53 mg of the title compound.

Workup

  1. temperatureThe mixture is heated over 20 hours to 110° C.
  2. customPhases are separated
  3. extractiontwo times extracted with ethylacetate
  4. concentrationThe combined organic phases are concentrated

Sources & evidence

ORD record
ord-44e8934f4845485487f818943ad8d73a
Source dataset
uspto-grants-2014_03
Patent number
US08680117B2

Reaction notes

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