Potassium Carbonate → 3-bromo-1-(3-bromomethyl-2-fluorobenzyl)-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

HRID 1831930

反応式

HRID 1831930 の反応式
[Br:1][C:2]1[C:3](=[O:18])[NH:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].C([O-])([O-])=O.[K+].[K+].[Br:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH2:33]Br)[C:28]=1[F:35]>CN(C=O)C>[Br:1][C:2]1[C:3](=[O:18])[N:4]([CH2:33][C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([CH2:26][Br:25])[C:28]=2[F:35])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 27360031,3-Bis(bromomethyl)-2-fluorobenzeneHCID 220508323-bromo-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

生成物 1

HCID 220504863-bromo-1-(3-bromomethyl-2-fluorobenzyl)-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one収率 49%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

To a solution of 3-bromo-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one (from Step 3, Example 74) (0.3 g, 0.95 mmol) in DMF (26 mL) was added K2CO3 (0.26 g, 1.9 mmol) and 2,6-bis(bromomethyl)fluorobenzene (1.6 g, 5.7 mmol), and the reaction mixture was stirred at 110° C. for 3 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was diluted with a 50% aqueous solution of brine, and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organics were washed with water, dried (Na2SO4), filtered, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent 99:1 to 95:5 methylene chloride/methanol) afforded 3-bromo-1-(3-bromomethyl-2-fluorobenzyl)-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one as an off-white solid (0.24 g, 49%): 1H NMR (300 MHz, CDCl3) δ 7.55-7.40 (m, 3H), 7.35-7.25 (m, 1H), 7.10-7.05 (m, 1H), 7.00-6.80 (m, 2H), 6.14 (d, J=6 Hz, 1H), 5.22 (s, 2H), 5.19 (s, 2H), 4.50 (s, 2H).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solvent was removed under reduced pressure
  3. additionThe residue was diluted with a 50% aqueous solution of brine
  4. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  5. washThe combined organics were washed with water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customPurification by flash column chromatography (silica, eluent 99:1 to 95:5 methylene chloride/methanol)

出典と根拠

ORDレコード
ord-44c3af60d63e4e86b83f1f367d27e8d4
出典データセット
uspto-grants-2006_06
特許番号
US07067540B2

関連ノート

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