Triethylamine → Ethyl 3-(3-fluoro-4-nitrophenyl)-3-oxopropanoate

HRID 73651

反応式

HRID 73651 の反応式
[CH2:1]([O:3][C:4](=[O:9])[CH2:5][C:6]([O-:8])=O)[CH3:2].[K+].[Mg+2].[Cl-].[Cl-].CCN(CC)CC.[F:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[N+:31]([O-:33])=[O:32])C(Cl)=O>C1COCC1.CCOC(C)=O>[F:21][C:22]1[CH:23]=[C:24]([C:6](=[O:8])[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:9])[CH:28]=[CH:29][C:30]=1[N+:31]([O-:33])=[O:32]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 27746563-Fluoro-4-nitrobenzoyl chlorideHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium Chloride

生成物 1

HCID 57955348Ethyl 3-(3-fluoro-4-nitrophenyl)-3-oxopropanoate収率 91%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
23 °C

実験手順

A 2 L round bottomed flask was fitted with a mechanical stir motor and nitrogen inlet. To a 10° C. solution of potassium 3-ethoxy-3-oxopropanoate (55.15 g, 324 mmol) in THF (500 mL) was added MgCl2 (38.56 g, 405 mmol) and Et3N (45 mL, 324 mmol). The reaction mixture was allowed to warm to 23° C. and stir for 3 h. A solution of 3-fluoro-4-nitrobenzoyl chloride (˜162 mmol) in THF (200 mL) was added. The reaction turned yellow instantly and a precipitate formed. THF (200 mL) was added to ensure that stirring was not impeded. TLC analysis indicated that the reaction had gone to completion however the reaction was allowed to stir over night. The reaction was quenched with 2 N HCl (1 L) and extracted with EtOAc (2×500 mL). The organic layer was washed with saturated NaHCO3 (500 mL), H2O (300 mL) and brine (200 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The desired product (37.65 g, 147 mmol) was isolated by flash column chromatography in 91% yield (1:1 Hex EtOAc) as a yellow solid as a mixture of keto (75%) and enol (25%) tautomers. 1H-NMR (DMSO-d6) Keto tautomer δ 8.29 (dd, J=8.6, 7.4 Hz, 1H), 8.10 (dd, J=11.6, 2.0 Hz, 1H), 7.94 (m, 1H), 4.30 (s, 2H), 4.11 (q, J=7.2 Hz, 2H), 1.17 (t, J=7.2 Hz, 3H); Enol tautomer δ 12.44 (br s, 1H), 8.22 (app t, J=8.2 Hz, 1H), 8.05 (dd, J=12.6, 2.0 Hz, 1H), 7.90 (m, 1H), 6.22 (s, 1H), 4.25 (q, J=7.2 Hz, 2H), 1.26 (t, J=7.2 Hz, 3H); LCMS RT=3.14 min; MS {M+H]+=311.0.

後処理

  1. customA 2 L round bottomed flask was fitted with a mechanical stir motor and nitrogen inlet
  2. customa precipitate formed
  3. stirringthat stirring
  4. stirringto stir over night
  5. customThe reaction was quenched with 2 N HCl (1 L)
  6. extractionextracted with EtOAc (2×500 mL)
  7. washThe organic layer was washed with saturated NaHCO3 (500 mL), H2O (300 mL) and brine (200 mL)
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-a141b749c6684d6c9efc9f670afad715
出典データセット
uspto-grants-2014_09
特許番号
US08829185B2

関連ノート

読み込み中…