Cesium carbonate → 3-[[3-(2-Methyl-5-pyridyloxy)phenyl][[3-(trifluoro-methoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

温度

105 °C

The 3-[(3-bromophenyl)[[3-(trifluoromethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol (500 mg, 1.1 mmol) product from EX-633B and 5-hydroxy-2-methylpyridine (262 mg, 2.4 mmol) were dissolved in dimethylacetamide (6 mL). Cs2CO3 (1.0 g, 3.1 mmol) and (CuCF3SO3)2C6H6 (150 mg) were added, and the mixture was heated to 105° C. for 96 h under an atmosphere of nitrogen, at which time HPLC analysis indicated that most of the starting materials had been consumed. After adding water, the reaction mixture was extracted with ether, and the ether extracts were washed with brine and dried over anhydrous MgSO4. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane (1:12) to give 326 mg (61%) of the desired 3-[[3-(2-methyl-5-pyridyloxy)phenyl][[3-(trifluoro-methoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a light amber oil, 99% pure by HPLC analysis. 1H NMR (CDCl3) δ 8.00 (s, 1H), 7.29 (t 1H), 6.99 (s, 1H), 7.02-7.15 (m, 5H), 6.46 (dd, 1H), 6.29 (t, 1H), 6.25 (dd, 1H), 4.88 (br s, 1H), 4.67 (ABq, 2H), 4.36 (m, 1H), 3.88 (dd, 1H), 3.56(dd, 1H), 2.49 (s, 3H). 19F NMR (CDCl3) δ −58.2, (s, 3F), −79.1 (d, 3F). HRMS calcd. for C23H20N2O3F6:487.1456 [M+H]+, found: 487.1425.

1. customhad been consumed
2. additionAfter adding water
3. extractionthe reaction mixture was extracted with ether
4. washthe ether extracts were washed with brine
5. dry with materialdried over anhydrous MgSO4
6. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane (1:12)

ORDレコード

ord-84cb4a29de4b408eb193f95ddfb7f964

出典データセット

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06710089B2