Ethanol → 6-Cyclopropyl-4-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
Reaction equation
C(O)C.[CH:4]1([C:7](=O)[CH2:8][C:9](=O)[CH3:10])[CH2:6][CH2:5]1.[C:13]([CH2:15][C:16]([NH2:18])=[O:17])#[N:14].N1CCCCC1>O>[CH:4]1([C:7]2[NH:18][C:16](=[O:17])[C:15]([C:13]#[N:14])=[C:9]([CH3:10])[CH:8]=2)[CH2:6][CH2:5]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 75 °C
Procedure
To a stirring solution of ethanol (5 mL) were suspended 1-cyclopropyl-1,3-butanedione (505 mg, 3.00 mmol) and cyanoacetamide (252 mg, 3.00 mmol), and the heterogenous contents heated until homogenous (ca. 75° C.). Next added piperidine (0.395 mL, 4.00 mmol), and the mixture was stirred with warming at reflux for 30 min. The reaction mixture was allowed to cool to room temperature, wherein precipitation ensued. The solid precipitate was filtered and set aside. The filtrate was concentrated in vacuo, and the oily residue treated with minimal EtOAc and then 10 mL hexanes to afford a 2nd crop of solid. The solid product crops were combined, suspended in water (7 mL), vigorously stirred, and vacuum filtered to afford a nearly white solid as 380 mg (73%). LCMS E-S (M+H)=175.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.01-1.09 (m, 2H), 1.28 (dd, J=8.59, 2.27 Hz, 2H), 1.95-2.01 (m, 1H), 2.43 (s, 3H), 5.82 (s, 1H).
Workup
- temperaturewith warming
- temperatureat reflux for 30 min
- temperatureto cool to room temperature
- customwherein precipitation
- filtrationThe solid precipitate was filtered
- concentrationThe filtrate was concentrated in vacuo
- additionthe oily residue treated with minimal EtOAc
- custom10 mL hexanes to afford a 2nd crop of solid
- stirringvigorously stirred
- filtrationvacuum filtered
- customto afford a nearly white solid as 380 mg (73%)
Sources & evidence
- ORD record
- ord-577ef3b2be53409ea4d109ecef681c5e
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637509B2
Reaction notes
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