Diethyl (ethoxymethylene)malonate → HCID 22397174, compound
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][N:3]=1.C([O:11][CH:12]=[C:13]([C:19](OCC)=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15])C.C1(OC2C=CC=CC=2)C=CC=CC=1>>[I:8][C:5]1[CH:6]=[CH:7][C:2]2[N:3]([CH:4]=1)[C:12](=[O:11])[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:19][N:1]=2Participants
Procedure
In a 3-necked round-bottom connected to a Dean-Stark trap, a solution of 2-amino-5-iodopyridine (Preparation 1, 500 mg) and diethyl ethoxymethylenemalonate (0.92 mL) is heated at 130° C. for 2 h. The reaction is cooled to room temperature. Diphenyl ether (5 mL) is added and the reaction is heated at 250° C. for 1 h. Upon cooling the mixture to room temperature, a solid precipitates and is filtered and washed with hexanes. The crude solid is adsorbed onto silica and chromatographed eluting with CH2Cl2 (2 L). Product-containing fractions are combined and concentrated to afford a solid. The crude product is recrystallized from CH2Cl2/hexanes to yield 251 mg (32%) of the title compound as a yellow solid. Physical characteristics: m.p. 166-168° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.24, 8.85, 8.38, 7.62, 4.27, 1.30; IR (drift) 1747, 1611, 1558, 1506, 1473, 1355, 1345, 1291, 1266, 1258, 1152, 1140, 1118, 840, 796 cm−1; MS (ESI+) m/z 345; Anal. found: C, 38.37; H, 2.48; N, 8.11.
Workup
- temperaturethe reaction is heated at 250° C. for 1 h
- temperatureUpon cooling the mixture to room temperature
- customa solid precipitates
- filtrationis filtered
- washwashed with hexanes
- customchromatographed
- washeluting with CH2Cl2 (2 L)
- concentrationconcentrated
- customto afford a solid
- customThe crude product is recrystallized from CH2Cl2/hexanes
Sources & evidence
- ORD record
- ord-b9fe1bbe26a74d37bf9582d1f49b3f2e
- Source dataset
- uspto-grants-2003_05
- Patent number
- US06559145B2
Reaction notes
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