4-Methylmorpholine → 3-(3-Hydroxy-4-methoxyphenyl)pentanedinitrile
Reaction equation
O=[CH:2][C:3]1[CH:11]=[CH:10][C:7]([O:8][CH3:9])=[C:5]([OH:6])[CH:4]=1.[C:12]([CH2:14]C(O)=O)#[N:13].[NH:18]1CCC[CH2:20][CH2:19]1.CN1CCOCC1>>[OH:6][C:5]1[CH:4]=[C:3]([CH:2]([CH2:14][C:12]#[N:13])[CH2:20][C:19]#[N:18])[CH:11]=[CH:10][C:7]=1[O:8][CH3:9]Participants
Procedure
To a 500 mL flask containing isovanillin (30.4 gm, 200 mmol) and cyanoacetic acid (68.0 gm, 800 mmol) was charged a solution consisting of 3.0 mL (30 mmol) piperidine and 151 mL N-methylmorpholine. The initially formed yellow slurry was warmed to mild reflux for 21 hours and then cooled to room temperature and concentrated on a rotary evaporator. The resulting brown oil was dissolved in 430 mL ethyl acetate (EtOAc), washed sequentially with water (H2O), five normal hydrochloric acid (5N HCl) and H2O and the combined aqueous washes back extracted with dichloroethane. Combination of the organic layers followed by solvent removal led to a thick orange oil which was crystallized from ethyl acetate/methylene chloride (EtOAc/CH2Cl2) to yield 38.3 gm of orange solids after filtration and drying. Recrystallization from EtOAc/diisopropyl ether gave 35.3 gm (82%) of light yellow solid, m.p. 90-92° C.
Workup
- additionwas charged a solution
- temperatureThe initially formed yellow slurry was warmed
- temperatureto mild reflux for 21 hours
- concentrationconcentrated on a rotary evaporator
- dissolutionThe resulting brown oil was dissolved in 430 mL ethyl acetate (EtOAc)
- washwashed sequentially with water (H2O), five normal hydrochloric acid (5N HCl) and H2O
- extractionthe combined aqueous washes back extracted with dichloroethane
- customCombination of the organic layers followed by solvent removal
- customwas crystallized from ethyl acetate/methylene chloride (EtOAc/CH2Cl2)
Sources & evidence
- ORD record
- ord-d42a5d8d5301416d830e2635d6dfbcb8
- Source dataset
- uspto-grants-2001_08
- Patent number
- US06274733B1
Reaction notes
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