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

HRID 990489

反応式

HRID 990489 の反応式
Br[C:2]1[CH:3]=[C:4]([N:8]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:27])([F:26])[F:25])[CH:18]=2)[CH2:9][CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.[OH:28][C:29]1[CH:30]=[CH:31][C:32]([CH3:35])=[N:33][CH:34]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[CH3:35][C:32]1[CH:31]=[CH:30][C:29]([O:28][C:2]2[CH:3]=[C:4]([N:8]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:27])([F:26])[F:25])[CH:18]=3)[CH2:9][CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=2)=[CH:34][N:33]=1

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 142752-Methyl-5-hydroxypyridineHCID 219187833-[(3-Bromophenyl)[[3-(trifluoromethoxy)phenyl]methyl]amino]1,1,1-trifluoro-2-propanol

生成物 1

HCID 235060733-[[3-(2-Methyl-5-pyridyloxy)phenyl][[3-(trifluoro-methoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol収率 61%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
105 °C

実験手順

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 (10 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.

後処理

  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)

出典と根拠

ORDレコード
ord-42ebd2d66e5d439f872283fa199172c9
出典データセット
uspto-grants-2002_10
特許番号
US06458849B1

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