proline dl-form → HCID 58392275、化合物

HRID 561403ノート

反応式

HRID 561403 の反応式
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([CH3:10])[CH:3]=1.C[C:12]1([CH3:20])[O:19][C:17](=[O:18])[CH2:16]C(=O)O1.N1CCCC1C(O)=O.[CH3:29][S:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]2[C:40]=1[NH:39][CH:38]=[CH:37]2>C(#N)C.[Cu].C(O)C.N1C=CC=CC=1>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]([C:37]2[C:36]3[C:40](=[C:32]([CH2:31][S:30][CH3:29])[CH:33]=[CH:34][CH:35]=3)[NH:39][CH:38]=2)[CH2:16][C:17]([O:19][CH2:12][CH3:20])=[O:18])=[C:4]([CH3:10])[CH:3]=1

参加物

9

反応物 4

HCID 614proline dl-formHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 27576584-Chloro-2-methylbenzaldehydeHCID 583921877-[(Methylsulfanyl)methyl]-1H-indole

生成物 1

HCID 58392275HCID 58392275、化合物

試薬・触媒・溶媒 4

HCID 23978Copper触媒HCID 702Ethanol溶媒HCID 1049Pyridine溶媒HCID 6342Acetonitrile溶媒

実験手順

1.44 g (9.31 mmol) of 4-chloro-2-methylbenzaldehyde, 1.34 g (9.31 mmol) of Meldrum's acid and 48.7 mg (0.42 mmol) of D,L-proline were added to a solution of 1.50 g (8.46 mmol) of the compound from Example 8A in 70 ml of acetonitrile. The reaction mixture was stirred at RT overnight. It was concentrated, and the residue was taken up in ethyl acetate, washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated. 3.43 g of a crude product were obtained and were introduced into 53 ml of pyridine and 14 ml of ethanol, and 4.8 mg (75 μmol) of copper powder were added. The reaction mixture was heated under reflux for 1 h. It was concentrated, and the residue was taken up in ethyl acetate, washed with 1N hydrochloric acid, dried over magnesium sulfate, filtered through silica gel and concentrated. The crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 1.68 g (49% of theory) of the title compound.

後処理

  1. concentrationIt was concentrated
  2. washwashed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custom3.43 g of a crude product were obtained
  7. additionwere added
  8. temperatureThe reaction mixture was heated
  9. temperatureunder reflux for 1 h
  10. concentrationIt was concentrated
  11. washwashed with 1N hydrochloric acid
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered through silica gel
  14. concentrationconcentrated
  15. customThe crude product was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

出典と根拠

ORDレコード
ord-b998de4b46d24570b1c7ab418e38e89f
出典データセット
uspto-grants-2011_11
特許番号
US08063234B2

反応ノート

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