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

HRID 1480287노트

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HRID 1480287 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

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온도
120 °C

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-bbeabb260d3946b39ccd2850af87b62e
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409866B2

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