1-Bromo-2-(trifluoromethoxy)benzene → (2-Amino-5-bromo-pyridin-3-yl)-(2-trifluoromethoxy-phenyl)-methanone

HRID 1820097노트

반응식

HRID 1820097 반응식
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][C:9]([F:12])([F:11])[F:10].C([Li])CCC.[NH2:18][C:19]1[N:30]=[CH:29][C:28]([Br:31])=[CH:27][C:20]=1[C:21](N(OC)C)=[O:22]>C1COCC1>[NH2:18][C:19]1[C:20]([C:21]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[O:8][C:9]([F:12])([F:11])[F:10])=[O:22])=[CH:27][C:28]([Br:31])=[CH:29][N:30]=1

참가 물질

5

반응물 3

HCID 27772661-Bromo-2-(trifluoromethoxy)benzeneHCID 596997242-amino-5-bromo-N-methoxy-N-methylnicotinamideHCID 178418339Butyllithium

생성물 1

HCID 59700140(2-Amino-5-bromo-pyridin-3-yl)-(2-trifluoromethoxy-phenyl)-methanone수율 52%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

To a flame-dried 100 ml round bottomed flask was added 1-bromo-2-(trifluoromethoxy)benzene (2.39 g, 9.9 mmol). The flask was fitted with a rubber septum, purged with nitrogen then charged with anhydrous THF (20 ml). The solution was cooled to −78° C. for 10 min, then a 2.5 M solution of n-butyl lithium in hexanes (3.9 ml, 9.8 mmol) was added dropwise over 3 minutes. The resulting solution was stirred at −78° C. for 40 minutes under nitrogen, then a solution of 739 mg (2.84 mmol) of 2-amino-5-bromo-N-methoxy-N-methyl-nicotinamide in 5 ml of THF was added dropwise over 3 minutes. The resulting red solution was allowed to warm to room temperature over 5 hours, then the reaction was quenched by addition of 10 ml of a saturated aqueous solution of ammonium chloride. Ethyl acetate (50 ml) was added, and the layers were separated. The aqueous fraction was extracted three times with ethyl acetate, and the combined organic fractions were washed with brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes gave 530 mg (52%) of (2-amino-5-bromo-pyridin-3-yl)-(2-trifluoromethoxy-phenyl)-methanone as a yellow-orange solid. 1H-NMR (CDCl3) δ=8.29 (d, 1H), 7.60 (m, 2H), 7.45 (t, 1H), 7.42 (m, 3H), 1.79 (br. s, 2H); MS m/z: 361 [MH]+.

후처리

  1. customThe flask was fitted with a rubber septum
  2. custompurged with nitrogen
  3. additionthen charged with anhydrous THF (20 ml)
  4. temperatureto warm to room temperature over 5 hours
  5. customthe reaction was quenched by addition of 10 ml of a saturated aqueous solution of ammonium chloride
  6. additionEthyl acetate (50 ml) was added
  7. customthe layers were separated
  8. extractionThe aqueous fraction was extracted three times with ethyl acetate
  9. washthe combined organic fractions were washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-93c52c655996476fb96f4071b3db085e
출처 데이터셋
uspto-grants-2009_10
특허 번호
US07601839B2

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