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

HRID 227692

反応式

HRID 227692 の反応式
[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

参加物

11

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 62652Cuprous chloride触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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]+

後処理

  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)

出典と根拠

ORDレコード
ord-b8582f7445d446d998ae72d62e71adb5
出典データセット
uspto-grants-2009_07
特許番号
US07560467B2

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