Acetone → (E)-4-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)but-3-en-2-one

HRID 1917473ノート

反応式

HRID 1917473 の反応式
[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]2[CH:13]=[CH:12][S:11][C:10]=2[CH:14]=O)[CH:6]=[CH:5][CH:4]=1.[CH3:16][C:17]([CH3:19])=[O:18].[OH-].[Na+].Cl>O>[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]2[CH:13]=[CH:12][S:11][C:10]=2/[CH:14]=[CH:16]/[C:17](=[O:18])[CH3:19])[CH:6]=[CH:5][CH:4]=1

参加物

6

反応物 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2 回HCID 579992833-(6-Methoxypyridin-2-yl)thiophene-2-carbaldehyde

生成物 1

HCID 57999307(E)-4-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)but-3-en-2-one収率 67%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
0 °C

実験手順

To a 500 mL recovery flask was added 3-(6-methoxypyridin-2-yl)thiophene-2-carbaldehyde (30C, 6.2 g, 28.3 mmol, 1.0 eq.), acetone (16.6 mL, 226 mmol, 8.0 eq.), and H2O (130 mL). Upon cooling to 0° C. in an ice bath, aqueous NaOH (5N, 6.2 mL, 31.1 mmol, 1.1 eq.) was added. The reaction mixture was stirred overnight while warming to room temperature. LC/MS monitoring showed the reaction to be −60% complete, so additional aqueous NaOH (5N, 1 mL, 5.0 mmol, 0.18 eq.) was added. After stirring for an additional 6 h the reaction was complete by LC/MS. The reaction mixture was neutralized with 3N aqueous HCl to a pH ˜8. The mixture was extracted with EtOAc (3×100 mL). The organic phases were combined and washed with saturated aqueous NaCl (100 mL). The combined aqueous phases were extracted with EtOAc (100 mL). The organic phases were combined and dried over anhydrous Na2SO4, filtered, and concentrated to give a black solid. The residue was purified via flash chromatography (60% CH2Cl2/Hex to 100% CH2Cl2) to give a yellow solid 30D (4.8 g, 67%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.29 (s, 3H) 3.96 (s, 3H) 6.59 (d, J=15.92 Hz, 1H) 6.84 (d, J=8.34 Hz, 1H) 7.41 (d, J=7.58 Hz, 1H) 7.60 (d, J=5.31 Hz, 1H) 7.75-7.88 (m, 2H) 8.71 (d, J=15.92 Hz, 1H). ESI-MS: m/z 260.3 (M+H)+.

後処理

  1. temperaturewhile warming to room temperature
  2. customthe reaction
  3. stirringAfter stirring for an additional 6 h the reaction
  4. extractionThe mixture was extracted with EtOAc (3×100 mL)
  5. washwashed with saturated aqueous NaCl (100 mL)
  6. extractionThe combined aqueous phases were extracted with EtOAc (100 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a black solid
  11. customThe residue was purified via flash chromatography (60% CH2Cl2/Hex to 100% CH2Cl2)

出典と根拠

ORDレコード
ord-86e44ec814624ff7b648afbc3cf4c44e
出典データセット
uspto-grants-2013_12
特許番号
US08618290B2

反応ノート

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