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

HRID 901440ノート

反応式

HRID 901440 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-554bae292540428b9e59eb52f7b4eaa8
出典データセット
uspto-grants-2008_04
特許番号
US07361763B2

反応ノート

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