Malonic Acid → 3-[1-(4-Methoxy benzenesulfonyl)-5-methoxy-1H-indol-3-yl]-acrylic acid

HRID 2100448Notes

Reaction equation

C[O:2][C:3](=[O:28])[CH2:4][CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH:7]=1.C(O)(=O)CC(O)=O.N1CCCCC1>N1C=CC=CC=1.C(OCC)(=O)C>[CH3:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([S:17]([N:8]2[C:9]3[C:14](=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)[C:6]([CH:5]=[CH:4][C:3]([OH:28])=[O:2])=[CH:7]2)(=[O:18])=[O:19])=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 1-(4-Methoxybenzenesulfonyl)-5-methoxy-1H-indole-3-carbaldehyde 5 (0.51 g, 1.5 mmol) dissolved in pyridine (10 mL), malonic acid (0.53 g, 5.1 mmol) and piperidine, (1 mL) were combined in a reaction vessel. The yellow solution was heated for 3 hours at 80° C. The reaction was allowed to cool to ambient temperature and diluted with 150 mL of ethyl acetate. The organic layer was washed with 1N HCl (6×50 mL) and saturated sodium chloride solution (1×50 mL). After drying over sodium sulfate, the organic layer was filtered through a pad of sodium sulfate and evaporated under reduced pressure to yield product 118 as an off-white solid. (0.521 g, 90%) 1HNMR (CDCl3) δ 7.86 (m, 5H), 7.2 (d, J=2.4 Hz, 1H), 7.0 (dd, J=2.8 Hz, 9.2 Hz, 1H), 6.91 (d, J=8.8 Hz, 2H), 6.46 (d, J=16, 1H), 3.87 (s, 3H, CH3) (M−1=386.2).

Workup

temperatureto cool to ambient temperature
washThe organic layer was washed with 1N HCl (6×50 mL) and saturated sodium chloride solution (1×50 mL)
dry with materialAfter drying over sodium sulfate
filtrationthe organic layer was filtered through a pad of sodium sulfate
customevaporated under reduced pressure

Sources & evidence

ORD record: ord-94771444fa444ceca9bfd876bdb0caaa
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07572806B2

Reaction notes

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