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

HRID 1017024

반응식

HRID 1017024 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
105 °C

실험 절차

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) δ8.00 (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 C23H20N2 F6: 487.1456 [M+H]+, found: 487.1425.

후처리

  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)

출처 및 근거

ORD 기록
ord-fe650fef1c7d49388ab77152235138e2
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06476057B1

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