Water → HCID 17985021, compound

HRID 2118076Notes

Reaction equation

HRID 2118076 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:19])([CH3:18])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)=[C:4]([O:20][CH3:21])[CH:3]=1.[NH2:22][C:23]1[CH:32]=[CH:31][C:30]([F:33])=[C:29]2[C:24]=1[CH:25]=[N:26][C:27]([CH3:34])=[N:28]2.O.C(OCC)(=O)C>C1(C)C=CC=CC=1.[Ti]>[F:14][C:13]([F:15])([F:16])[C:10]([CH:11]=[N:22][C:23]1[CH:32]=[CH:31][C:30]([F:33])=[C:29]2[C:24]=1[CH:25]=[N:26][C:27]([CH3:34])=[N:28]2)([OH:17])[CH2:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[O:20][CH3:21])([CH3:19])[CH3:18]

Participants

7

Reactant 4

HCID 962Water2×HCID 8857Ethyl AcetateHCID 179850558-Fluoro-2-methylquinazolin-5-amineHCID 219489374-(4-Chloro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanal

Product 1

HCID 17985021HCID 17985021, compoundYield 90.1%

Reagents, catalysts & solvents 2

HCID 23963TitaniumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

2.40 g (7.39 mmol) of rac-4-(4-chloro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)-pentanal is dissolved with 1.30 g (7.34 mmol) of 5-amino-8-fluoro-2-methylquinazoline in 30 ml of toluene, and 3.10 ml (14.7 mmol) of titanium tetraethylate is added at room temperature. The mixture is stirred for 3 hours at 105° C. After cooling, the mixture is added to water, stirred for several minutes, suctioned off on diatomaceous earth, rewashed with ethyl acetate and water, and the phases are separated. The aqueous phase is extracted several times with ethyl acetate, and the combined organic phases are washed with saturated NaCl solution and dried with sodium sulfate. The solvent is removed in a rotary evaporator, and the crude product is chromatographed on silica gel (eluant hexane/ethyl acetate 4:1). 3.20 g (90%) of the desired compound is isolated.

Workup

  1. additionis added at room temperature
  2. temperatureAfter cooling
  3. stirringstirred for several minutes
  4. customthe phases are separated
  5. extractionThe aqueous phase is extracted several times with ethyl acetate
  6. washthe combined organic phases are washed with saturated NaCl solution
  7. dry with materialdried with sodium sulfate
  8. customThe solvent is removed in a rotary evaporator
  9. customthe crude product is chromatographed on silica gel (eluant hexane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-73d37f121153463cbdb1e039c21deb8b
Source dataset
uspto-grants-2008_10
Patent number
US07442794B2

Reaction notes

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