Cesium carbonate → 5-(3,3-Difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)picolinonitrile

HRID 1480287ノート

反応式

HRID 1480287 の反応式
Br[C:2]1[C:3]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.Cl.[F:17][C:18]1([F:22])[CH2:21][NH:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:17][C:18]1([F:22])[CH2:21][N:20]([C:2]2[C:3]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=2)[CH2:19]1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27582473,3-Difluoroazetidine hydrochlorideHCID 902033795-Bromo-4-(2,2,2-trifluoroethoxy)picolinonitrile

生成物 1

HCID 902032995-(3,3-Difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)picolinonitrile収率 78.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
120 °C

実験手順

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carbonitrile (example 78c, 587 mg, 2.09 mmol) in dry toluene (10 ml) in a schlenk tube was added 3,3-difluoroazetidine hydrochloride (298 mg, 2.3 mmol), cesium carbonate (1.36 g, 4.18 mmol), palladium diacetate (46.9 mg, 209 μmol) and BINAP (130 mg, 209 μmol). The reaction mixture was stirred at 120° C. for 1 hour. The reaction mixture was filtered over a pad of celite and the filtrate was diluted with ethylacetate. The organic phase was extracted with a 1M aqueous solution of sodium bicarbonate. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (480 mg, 78%). MS (ESI, m/z): 294.2 (M+H+).

後処理

  1. filtrationThe reaction mixture was filtered over a pad of celite
  2. additionthe filtrate was diluted with ethylacetate
  3. extractionThe organic phase was extracted with a 1M aqueous solution of sodium bicarbonate
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated down to dryness
  6. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

出典と根拠

ORDレコード
ord-bbeabb260d3946b39ccd2850af87b62e
出典データセット
uspto-grants-2016_08
特許番号
US09409866B2

反応ノート

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