Diazomethane → Ethyl 2-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinolin-6-yl)cyclopropanecarboxylate

HRID 1023168Notes

Reaction equation

HRID 1023168 reaction equation
[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[CH:13][C:14](/[CH:18]=[CH:19]/[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:25])=[CH:5][CH:4]=1.[N+](=[CH2:30])=[N-]>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[CH:13][C:14]([CH:18]4[CH2:30][CH:19]4[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:25])=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 9550DiazomethaneHCID 86680408(E)-ethyl 3-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinolin-6-yl)acrylate

Product 1

HCID 86680409Ethyl 2-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinolin-6-yl)cyclopropanecarboxylateYield 57%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a stirred solution of (E)-ethyl 3-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinolin-6-yl)acrylate (1.2 g, 3.21 mmol) in diethyl ether (50 mL) was added palladium (II) acetate (0.031 g, 0.138 mmol). The reaction mixture was cooled to −10° C., and a cold solution of diazomethane (1.351 g, 32.1 mmol) in ether (generated from aqueous KOH (8 g, 143 mmol) and 1-methyl-1-nitrosourea (4 g, 38.8 mmol) at −15° C.) was added. The reaction mixture was stirred at room temperature for 12 h. The reaction mixture was filtered through celite, diluted with diethyl ether, and washed with water and saturated NaCl solution. The organic layer was dried over sodium sulfate, concentrated, and purified by flash chromatography on silica gel column using 15% ethyl acetate in hexane to give ethyl 2-(1-(4-methoxybenzyl)-2-oxo-1,2-dihydroquinolin-6-yl)cyclopropanecarboxylate as a yellow gum (510 mg, 57%). 1H NMR 400 MHz, CDCl3: δ 1.29 (t, J=4.80 Hz, 3H), 1.31 (d, J=4.80 Hz, 1H), 1.62 (d, J=4.80 Hz, 1H), 1.84-1.89 (m, 1H), 2.51-2.56 (m, 1H), 3.76 (d, J=2.80 Hz, 3H), 3.98 (q, J=174.00 Hz, 2H), 5.47 (s, 2H), 6.77-6.83 (m, 3H), 7.13-7.28 (m, 5H), 7.66 (d, J=9.60 Hz, 1H).

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. additiondiluted with diethyl ether
  3. washwashed with water and saturated NaCl solution
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by flash chromatography on silica gel column

Sources & evidence

ORD record
ord-5c95e3393ee44943b39a4abd2ddd8299
Source dataset
uspto-grants-2014_05
Patent number
US08722670B2

Reaction notes

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