Oxalyl chloride → Ethyl 3-(4-methoxy-2-(methylthio)pyrimidin-5-yl)-3-oxopropanoate

HRID 1160435ノート

反応式

HRID 1160435 の反応式
[CH3:1][O:2][C:3]1[C:8]([C:9]([OH:11])=O)=[CH:7][N:6]=[C:5]([S:12][CH3:13])[N:4]=1.[C:14](Cl)(=[O:18])[C:15](Cl)=O.[Mg+2].[Cl-].[Cl-].C([O-])(=O)[CH2:24][C:25]([O-])=[O:26].C([Mg+2])C>C1(C)C=CC=CC=1.C1COCC1.O.CCOC(C)=O>[CH3:1][O:2][C:3]1[C:8]([C:9](=[O:11])[CH2:24][C:25]([O:18][CH2:14][CH3:15])=[O:26])=[CH:7][N:6]=[C:5]([S:12][CH3:13])[N:4]=1

参加物

9

反応物 4

HCID 65578Oxalyl chlorideHCID 5360315Magnesium ChlorideHCID 128290034-Methoxy-2-(methylsulfanyl)pyrimidine-5-carboxylic acidHCID 178525631HCID 178525631、化合物

生成物 1

HCID 25222986Ethyl 3-(4-methoxy-2-(methylthio)pyrimidin-5-yl)-3-oxopropanoate収率 52.4%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A solution of 4-methoxy-2-(methylthio)pyrimidine-5-carboxylic acid (10.92 g, 54.6 mmol) and oxalyl chloride (19.0 mL, 217.8 mmol) in toluene (100 mL) was heated at 100° C. for 1 h. The solvent was removed under reduced pressure and the crude acid chloride was used without purification in the next step. To a solution of MgCl2 (7.80 g, 81.9 mmol) and ethyl magnesium malonate (14.10 g, 82.6 mmol) in THF (100 mL) was added the above acid chloride in THF (100 mL) at 0° C. followed by TEA (15.0 mL, 107.6 mmol). The reaction mixture was stirred at 0° C. for 30 min and at rt for 2 h. EtOAc (200 mL) and H2O (100 mL) were added and stirred for additional 30 min. The layers were separated and the organic layer was washed with brine (100 mL), dried over Na2SO4, and concentrated. The crude was purified by flash chromatography (15% EtOAc/hexanes) to yield the desired compound as a white solid (7.73 g, 52%). MS (m/z): 271 (MH+). 1H NMR (CDCl3) δ: 12.65 (s, 1H×⅔), 8.85 (s, 1H×⅓), 8.84 (s, 1H×⅔), 6.03 (s, 1H×⅔), 4.26 (q, 2H×⅔), 4.19 (q, 2H×⅓), 4.10 (s, 3H×⅔), 4.09 (s, 3H×⅓), 3.92 (s, 2H×⅓), 2.60 (s, 3H×⅓), 2.59 (s, 3H×⅔), 1.34 (t, 3H×⅔), 1.26 (3H×⅓).

後処理

  1. customThe solvent was removed under reduced pressure
  2. customthe crude acid chloride was used without purification in the next step
  3. stirringstirred for additional 30 min
  4. customThe layers were separated
  5. washthe organic layer was washed with brine (100 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude was purified by flash chromatography (15% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-3350cccbda1d4063ab1a4280be5f4e04
出典データセット
uspto-grants-2010_10
特許番号
US07816406B2

反応ノート

読み込み中…