Acetic Acid → Methyl 4-(4-fluorophenyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

HRID 227692

반응식

HRID 227692 반응식
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.CO[CH:12](OC)[CH2:13][C:14]([O:16][CH3:17])=[O:15].[NH2:20][C:21]([NH2:23])=[O:22].C(O)(=O)C.B(F)(F)F.CCOCC.C([O-])(O)=O.[Na+]>O.[Cu]Cl.C(OCC)(=O)C.C1COCC1>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][NH:23][C:21](=[O:22])[NH:20]2)=[CH:4][CH:3]=1

참가 물질

11

반응물 6

HCID 176Acetic AcidHCID 1176UreaHCID 8000Boron trifluoride etherateHCID 680234-FluorobenzaldehydeHCID 81924Methyl 3,3-dimethoxypropionateHCID 516892Sodium Bicarbonate

생성물 1

HCID 57755876Methyl 4-(4-fluorophenyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate수율 11.5%

시약·촉매·용매 4

HCID 62652Cuprous chloride촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

A round bottom flask was charged with 4-fluorobenzaldehyde (2.00 mL, 18.6 mmol, 1 equiv), methyl 3,3-dimethoxypropionate (2.49 mL, 18.6 mmol, 1 equiv), urea (1.68 g, 28.0 mmol, 1.5 equiv), and copper (I) chloride (184 mg, 1.86 mmol, 0.1 equiv). THF (18.6 mL) was added, followed by acetic acid (0.110 mL, 1.86 mmol, 0.1 equiv) and BF3.OEt2 (3.07 mL, 24.2 mmol, 1.3 equiv). The slurry was heated to reflux for 24 hours, then stirred at room temperature for an additional 36 hours. The mixture was diluted with water and carefully neutralized with satd. NaHCO3. Ethyl acetate was added, and the biphasic solution was filtered through celite. The layers were separated, and the aqueous layer was washed with an additional portion of ethyl acetate. The combined organic extracts were washed with satd. NaCl, dried over Na2SO4, filtered and concentrated to a foamy solid. The residue was purified by flash chromatography (50% Ch2Cl2/ethyl acetate) to provide 535 mg of the product as an off-white powder (535 mg, 11%). NMR 1H NMR (400 MHz, DMSO-D6) δ ppm 9.25 (d, J=5 Hz, 1H), 7.72 (br s, 1H), 7.30-7.26 (m, 3H), 7.17 (t, J=8.9 Hz, 2H), 5.14 (d, J=3 Hz, 1H), 3.56 (s, 3H) MS m/z 251 [M+H]+

후처리

  1. temperatureThe slurry was heated
  2. temperatureto reflux for 24 hours
  3. filtrationthe biphasic solution was filtered through celite
  4. customThe layers were separated
  5. washthe aqueous layer was washed with an additional portion of ethyl acetate
  6. washThe combined organic extracts were washed with satd
  7. dry with materialNaCl, dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a foamy solid
  10. customThe residue was purified by flash chromatography (50% Ch2Cl2/ethyl acetate)

출처 및 근거

ORD 기록
ord-b8582f7445d446d998ae72d62e71adb5
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07560467B2

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