4-Chlorobenzaldehyde → 4-(4-Chlorophenyl)-2-morpholin-4-yl-6-oxo-4,6-dihydrothieno[2,3-c]furan-3-carbonitrile

HRID 1615510ノート

反応式

HRID 1615510 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([C:14]([OH:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].C([Li])CCC.[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1>C1COCC1>[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]2[O:15][C:14](=[O:16])[C:5]3[S:6][C:7]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)=[C:3]([C:1]#[N:2])[C:4]2=3)=[CH:25][CH:24]=1

参加物

5

反応物 3

HCID 77264-ChlorobenzaldehydeHCID 686278674-Cyano-5-morpholin-4-ylthiophene-2-carboxylic acidHCID 178418339Butyllithium

生成物 1

HCID 569713544-(4-Chlorophenyl)-2-morpholin-4-yl-6-oxo-4,6-dihydrothieno[2,3-c]furan-3-carbonitrile収率 13.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-70 °C

実験手順

A solution of 4-cyano-5-morpholin-4-ylthiophene-2-carboxylic acid (0.1 g, 0.42 mmol) in anhydrous THF (1.5 mL) was cooled down to −70° C. To this cooled solution was added a 2.5 M solution of n-butyl lithium in hexanes (0.672 mL, 1.68 mmol) dropwise under nitrogen. The resulting solution was stirred at −70° C. for 2 h and 4-chlorobenzaldehyde (0.142 mL, 1.26 mmol) was added. The reaction mixture was stirred at −70° C. for a further 2 h and was quenched with water. The mixture was concentrated to a small volume and the aqueous residue was washed with EtOAc. The aqueous solution was separated, acidified with 1N HCl and extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by column chromatography to give the title compound (0.020 g, 13%), LCMS: (FA) ES+ 361, 363. 1H NMR (400 MHz, d6-DMSO) δ: 7.54 (d, J=8.48 Hz, 2H), 7.38 (d, J=8.48 Hz, 2H), 6.72 (s, 1H), 3.77-3.73 (m, 4H), 3.65-3.60 (m, 4H)

後処理

  1. stirringThe reaction mixture was stirred at −70° C. for a further 2 h
  2. customwas quenched with water
  3. concentrationThe mixture was concentrated to a small volume
  4. washthe aqueous residue was washed with EtOAc
  5. customThe aqueous solution was separated
  6. extractionextracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by column chromatography

出典と根拠

ORDレコード
ord-388760b637dc4866bee0d2a18457eb52
出典データセット
uspto-grants-2014_07
特許番号
US08765746B2

反応ノート

読み込み中…