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Water → ethyl 5-cyclopropyl-1-(4-ethoxy-2,6-difluorobenzyl)-4-methyl-1H-pyrazole-3-carboxylate

HRID 1484680
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HRID 1484680 반응식
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:5]=2[CH3:14])[CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:18][C:19]1[C:24]([F:25])=[CH:23][C:22]([O:26][CH2:27][CH3:28])=[CH:21][C:20]=1[F:29].O>C1COCC1>[CH:1]1([C:4]2[N:8]([CH2:18][C:19]3[C:20]([F:29])=[CH:21][C:22]([O:26][CH2:27][CH3:28])=[CH:23][C:24]=3[F:25])[N:7]=[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:5]=2[CH3:14])[CH2:2][CH2:3]1
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참가 물질

6

반응물 4

HCID 962WaterHCID 24758Sodium hydrideHCID 467376162-(Bromomethyl)-5-ethoxy-1,3-difluorobenzeneHCID 89648788Ethyl 5-cyclopropyl-4-methyl-1H-pyrazole-3-carboxylate

생성물 1

HCID 89649016ethyl 5-cyclopropyl-1-(4-ethoxy-2,6-difluorobenzyl)-4-methyl-1H-pyrazole-3-carboxylate수율 89%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매
2회

실험 절차

46.9 g of ethyl 5-cyclopropyl-4-methyl-1H-pyrazole-3-carboxylate 1-15-1 (266 mmol, 1.0 eq.) in 588 mL THF were cooled to 0° C. and 11.6 g sodiumhydride (60%, 290 mmol, 1.2 eq.) were added in small portions. The resulting suspension was diluted with 250 mL THF. 66.7 g 2-(bromomethyl)-5-ethoxy-1,3-difluorobenzene (266 mmol, 1.1 eq., commercially available) were added slowly. The reaction mixture was stirred at rt for 2 hours. 300 mL water was added and the THF was evaporated in vacuum. The aqueous residue was extracted with ethylacetate three times. The combined organic layers were dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to provide 79.8 g (195 mmol, 81%) of 89% pure target compound.

후처리

  1. customthe THF was evaporated in vacuum
  2. extractionThe aqueous residue was extracted with ethylacetate three times
  3. dry with materialThe combined organic layers were dried over a silicone
  4. filtrationfilter
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography

출처 및 근거

ORD 기록
ord-2d44bf17dea048938f76069536fa88dd
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09422268B2

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