Malonic Acid → 3-{2-[3-(Quinolin-2-ylmethoxy)-benzyloxy]-phenyl}-acrylic acid

HRID 892181Notes

Reaction equation

[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:14]=[C:15]([CH:26]=[CH:27][CH:28]=1)[CH2:16][O:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]=O.C(O)(=O)[CH2:30][C:31]([OH:33])=[O:32].N1CCCCC1>N1C=CC=CC=1>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:14]=[C:15]([CH:26]=[CH:27][CH:28]=1)[CH2:16][O:17][C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]=[CH:30][C:31]([OH:33])=[O:32]

Participants

Conditions

Temperature: 85 °C

Procedure

2-[3-(Quinolin-2-ylmethoxy)-benzyloxy]-benzaldehyde (110 mg, 0.3 mmol, example 56) is dissolved in pyridine (1 mL). Malonic acid (63 mg, 0.6 mmol) and piperidine (10 μL, 0.1 mmol) are added and the contents are heated to 85° C. for 2 hrs, then at 110° C. for another 2 hrs. The reaction is cooled and placed under a nitrogen stream at 40° C. to remove the pyridine. A small amount of toluene is added and the contents are again placed under a nitrogen stream at 40° C. (repeat). The crude material is purified on silica gel by flash chromatography (silica, 2.5% methanol in dichloromethane) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.33 (d, 1H), 8.21–8.16 (m, 2H), 7.81–7.70 (m, 3H), 7.56–7.50 (m, 2H), 7.37–7.25 (m, 3H), 7.03–6.93 (m, 4H), 6.50 (d, 1H), 5.48 (s, 2H), 5.14 (s, 2H); MS (ion spray) 412 (M+H)+.

Workup

temperatureThe reaction is cooled
customat 40° C.
customto remove the pyridine
additionA small amount of toluene is added
customat 40° C.
customThe crude material is purified on silica gel by flash chromatography (silica, 2.5% methanol in dichloromethane)

Sources & evidence

ORD record: ord-e80f982d165441a790011ce87428323f
Source dataset: uspto-grants-2006_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07005440B1

Reaction notes

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