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

HRID 1615510노트

반응식

HRID 1615510 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-70 °C

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-388760b637dc4866bee0d2a18457eb52
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765746B2

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