Ethyl iodoacetate → Ethyl 4-cyano-3-(2,4-dichlorophenyl)-5-morpholin-4-ylthiophene-2-carboxylate
Reaction equation
[N:1]1([C:7](=[S:11])[CH2:8][C:9]#[N:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:12][C:13]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:14]=1[C:15](Cl)=O.CCN(C(C)C)C(C)C.I[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35]>C(#N)C>[C:9]([C:8]1[C:15]([C:14]2[CH:18]=[CH:19][C:20]([Cl:22])=[CH:21][C:13]=2[Cl:12])=[C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[S:11][C:7]=1[N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)#[N:10]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 3-morpholin-4-yl-3-thioxopropanenitrile (0.150 g, 0.88 mmol) in anhydrous ACN (1.2 mL) was cooled to 0° C. To this cooled solution was added of 2,4-dichlorobenzoyl chloride (0.149 mL, 1.06 mmol) and DIPEA (0.161 mL, 0.93 mmol). The mixture was allowed to stir at rt under nitrogen for 15 min before ethyl iodoacetate (0.10 mL, 0.93 mmol) and DIPEA (0.161 mL, 0.93 mmol) were added. The reaction mixture was subjected to MWI at 140° C. for 10 min. The mixture was allowed to cool and was concentrated. The residue was purified by column chromatography to give ethyl 4-cyano-3-(2,4-dichlorophenyl)-5-morpholin-4-ylthiophene-2-carboxylate (78) (0.1 g, 28%). LCMS: (AA) ES+ 411.09. 1H NMR (400 MHz, CDCl3) δ: 7.49 d, 1H), 7.33 (dd, 1H), 7.20 (d, 1H), 4.08-4.16 (m, 2H), 3.85-3.89 (m, 4H), 3.63-3.66 (m, 4H) and 1.12 (t, 3H).
Workup
- additionwere added
- temperatureto cool
- concentrationwas concentrated
- customThe residue was purified by column chromatography
Sources & evidence
- ORD record
- ord-2a1af50d26f54388abc6e7224476bd10
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09029411B2
Reaction notes
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