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

HRID 73651

반응식

HRID 73651 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매

반응 조건

온도
23 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-a141b749c6684d6c9efc9f670afad715
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829185B2

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