Sodium Carbonate → ethyl 1-cyclopropyl-8-(4-methylphenyl)-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

HRID 1854855Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[N:14]2[C:9]([C:10]([CH3:18])=[C:11](Cl)[CH:12]=[CH:13]2)=[C:8]([CH:19]2[CH2:21][CH2:20]2)[CH:7]=1)=[O:5])[CH3:2].[CH3:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:19]1([C:8]2[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[C:15](=[O:16])[N:14]3[C:9]=2[C:10]([CH3:18])=[C:11]([C:26]2[CH:27]=[CH:28][C:23]([CH3:22])=[CH:24][CH:25]=2)[CH:12]=[CH:13]3)[CH2:21][CH2:20]1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester (120 mg, 0.400 mmol), 4-methyl-phenyl boronic acid (65 mg, 0.48 mmol), (Ph3P)2PdCl2 (28 mg, 0.040 mmol), and Na2CO3 (190 mg in 0.8 mL of water, 1.80 mmol) in THF (5 mL) was degassed 3 times under N2 and heated to 80° C. overnight. The reaction mixture was diluted with ethyl acetate (50 mL), and washed with water (2×20 mL). The organic phase was separated, dried, and concentrated. The residue was purified by flash silica column chromatography (hexane:ethyl acetate, 1:2) to afford the title compound as a yellow solid (90 mg, 62%). ESI-MS m/z: 362 (M+H)+.

Workup

customwas degassed 3 times under N2
additionThe reaction mixture was diluted with ethyl acetate (50 mL)
washwashed with water (2×20 mL)
customThe organic phase was separated
customdried
concentrationconcentrated
customThe residue was purified by flash silica column chromatography (hexane:ethyl acetate, 1:2)

Sources & evidence

ORD record: ord-62fc51e285fb4612baaf280920617201
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962842B2

Reaction notes

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