Sodium Bicarbonate → (S)-methyl 2-(4-(2-chlorophenoxy)-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)-4-methylpentanoate

HRID 18997

反応式

HRID 18997 の反応式
Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]([CH2:7][CH:8]([CH3:10])[CH3:9])[NH2:6].C(=O)(O)[O-].[Na+].C([O:19][C:20](=O)/[CH:21]=[C:22](/[O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[Cl:32])\[CH2:23]Br)C>C(O)C>[CH3:2][O:3][C:4](=[O:11])[C@@H:5]([N:6]1[CH2:23][C:22]([O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[Cl:32])=[CH:21][C:20]1=[O:19])[CH2:7][CH:8]([CH3:10])[CH3:9]

参加物

5

反応物 3

HCID 516892Sodium BicarbonateHCID 2723695Leucine methyl ester hydrochlorideHCID 66895331(E)-4-bromo-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester

生成物 1

HCID 57346985(S)-methyl 2-(4-(2-chlorophenoxy)-2-oxo-2,5-dihydro-1H-pyrrol-1-yl)-4-methylpentanoate収率 147.2%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

To a solution of (L)-leucine methyl ester hydrochloride salt (152.6 g, 0.840 mol) in ethanol (200 proof denatured, 2500 mL) was added sodium bicarbonate (115.3 g, 1.37 mol) at room temperature and the resulting mixture stirred for 15 min. To this mixture was added (E)-4-bromo-3-(2-chloro-phenoxy)-but-2-enoic acid ethyl ester (87.7% pure by HPLC, 200 g, 0.549 mol). The resulting cloudy solution was heated to reflux and approx. 500 mL of solvent was removed via a Dean Stark trap before reflux was continued overnight. To this solution was added glacial acetic acid (200 mL) and the solution was heated to reflux for an additional 2 h. The reaction mixture was cooled to room temperature and methyl t-butyl ether (2.7 L) and water (2 L) were added. The mixture was separated and the organic phase washed with a 20% sodium chloride solution (2 L). The solution was evaporated, the residue treated with toluene (2 L) and evaporated again to give (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (83.3% pure by HPLC, 273 g) as a dark orange oil.

後処理

  1. temperatureThe resulting cloudy solution was heated
  2. temperatureto reflux
  3. customapprox. 500 mL of solvent was removed via a Dean Stark trap
  4. temperaturebefore reflux
  5. waitwas continued overnight
  6. additionTo this solution was added glacial acetic acid (200 mL)
  7. temperaturethe solution was heated
  8. temperatureto reflux for an additional 2 h
  9. additionmethyl t-butyl ether (2.7 L) and water (2 L) were added
  10. customThe mixture was separated
  11. washthe organic phase washed with a 20% sodium chloride solution (2 L)
  12. customThe solution was evaporated
  13. additionthe residue treated with toluene (2 L)
  14. customevaporated again

出典と根拠

ORDレコード
ord-a6de3ae945c34d24aef1939a0a6aff75
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

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