Diethyl (ethoxymethylene)malonate → Ethyl 2-((Acetyloxy)methyl)-8-iodo-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]-quinoline-5-carboxylate
Reaction equation
C(O[CH:4]=[C:5]([C:11]([O:13]CC)=O)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.[C:16]([O:19][CH2:20][CH:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([I:30])[CH:27]=2)[NH:22]1)(=[O:18])[CH3:17]>>[C:16]([O:19][CH2:20][CH:21]1[N:22]2[C:23]3[C:24]([C:11](=[O:13])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4]2)=[CH:25][C:26]([I:30])=[CH:27][C:28]=3[CH2:29]1)(=[O:18])[CH3:17]Participants
Conditions
- Temperature
- 120 °C
Procedure
A mixture of diethyl ethoxymethylenemalonate (2.73 mL) and (5-iodo-2,3-dihydro-1H-indol-2-yl)methyl acetate (Preparation 8, 3.90 g) is heated to 120° C. under a stream of nitrogen. After starting material is consumed, the mixture is cooled and diluted with EtOAc. The crude product is chromatographed eluting with 20, 40, and 60% EtOAc in heptane (500 mL each) to give 5.28 g (88%) of the corresponding enamine as a brown oil. A portion of this material (4.61 g) is dissolved in Eaton's Reagent (10 mL) and heated to 80° C. for 1 h. Upon cooling, the crude mixture is poured into a cold beaker and a 50% NaOH solution is slowly added until pH=7. The cloudy solution is then poured into CH2Cl2. The organic layer is separated and washed with brine, dried (Na2SO4), filtered, and concentrated to give a brown solid. The crude product is chromatographed eluting with 0-4% methanol in CH2Cl2 to give 880 mg (21%) of the title compound as a brown solid. Physical characteristics: MS (ESI+) m/z 442 (M+H)+, 464 (M+Na)+.
Workup
- customis consumed
- temperaturethe mixture is cooled
- additiondiluted with EtOAc
- customThe crude product is chromatographed
- washeluting with 20, 40, and 60% EtOAc in heptane (500 mL each)
Sources & evidence
- ORD record
- ord-cda75b414a9c4d17a8ce39244a81dc47
- Source dataset
- uspto-grants-2003_09
- Patent number
- US06624159B2
Reaction notes
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