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

HRID 1362486

반응식

HRID 1362486 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 76524Titanium tetraethoxide촉매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-72ee268652524c0587fc061c1fb67a7b
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07880042B2

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