Water → 4-(3-Fluoro-2-methoxyphenyl)-1-[(2-methylquinolin-5-yl)imino]-2-(trifluoromethyl)pentan-2-ol

HRID 1362486Notes

Reaction equation

HRID 1362486 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:18])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)=[C:4]([O:19][CH3:20])[C:3]=1[F:21].[NH2:22][C:23]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:24]=1[CH:25]=N[C:27]([CH3:33])=[N:28]2.O.[C:35]1(C)C=CC=CC=1>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[F:21][C:3]1[C:4]([O:19][CH3:20])=[C:5]([CH:8]([CH3:18])[CH2:9][C:10]([C:13]([F:14])([F:15])[F:16])([OH:17])[CH:11]=[N:22][C:23]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:24]=2[CH:25]=[CH:35][C:27]([CH3:33])=[N:28]3)[CH:6]=[CH:7][CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1140TolueneHCID 179850582-Methylquinazolin-5-amineHCID 866153194-(4-Chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal

Product 1

HCID 669694754-(3-Fluoro-2-methoxyphenyl)-1-[(2-methylquinolin-5-yl)imino]-2-(trifluoromethyl)pentan-2-ol

Reagents, catalysts & solvents 1

HCID 76524Titanium tetraethoxideCatalyst

Procedure

100 mg (0.3 mmol) of 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal, 48 mg (0.3 mmol) of 5-amino-2-methylquinazoline and 0.1 ml of titanium tetraethoxide are stirred in 9 ml of toluene at 100° C. for 2 h. After cooling, the mixture is poured into water and stirred vigorously. The suspension is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate. The phases of the filtrate are separated and extraction is carried out again with ethyl acetate. The extracts are dried over sodium sulphate and the solvent is removed in vacuo to give 130 mg of 4-(3-fluoro-2-methoxyphenyl)-1-[(2-methylquinolin-5-yl)imino]-2-(trifluoromethyl)pentan-2-ol as a crude product. 130 mg of the crude imine in 6 ml of CH2Cl2 are admixed dropwise at −30° C. with 3 ml (3 mmol) of a 1 M of boron tribromide solution. The batch is allowed to warm to −5° C. over 3 hours. It is admixed with saturated NaHCO3 solution, the phases are separated, the aqueous phase is extracted with ethyl acetate and the combined organic phases are dried (Na2SO4) and concentrated in vacuo. Column chromatography on silica gel (hexane/ethyl acetate 0-75%) yields 30 mg as a mixture of the title compound and 5α,6α,8β)-3-chloro-2-fluoro-8-methyl-5-[(2-methylquinazolin-5-yl)amino]-6-(trifluoromethyl)-5,6,7,8-tetrahydronaphthalene-1,6-diol (Ex. 23). Preparative thin-layer chromatography on amine phase (Merck) with ethyl acetate/methanol/triethylamine 25:3:1 yields 5 mg of product.

Workup

  1. temperatureAfter cooling
  2. filtrationThe suspension is filtered through Celite
  3. washthe filter bed being rinsed thoroughly with ethyl acetate
  4. customThe phases of the filtrate are separated
  5. extractionextraction
  6. dry with materialThe extracts are dried over sodium sulphate
  7. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-72ee268652524c0587fc061c1fb67a7b
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Reaction notes

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