Cesium carbonate → Methyl 7-(2,2-dimethyl-propionylamino)-1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoline-6-carboxylate

HRID 715968Notes

Reaction equation

Br[C:2]1[C:3]([CH2:19][CH2:20][CH:21]2[CH2:25][CH2:24][CH2:23][NH:22]2)=[C:4]([C:9]([NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:15][C:14]([CH3:17])([CH3:16])[C:13]([NH:12][C:9]1[CH:10]=[CH:11][C:2]2[N:22]3[CH2:23][CH2:24][CH2:25][CH:21]3[CH2:20][CH2:19][C:3]=2[C:4]=1[C:5]([O:7][CH3:8])=[O:6])=[O:18]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl 3-bromo-6-(2,2-dimethylpropionylamino)-2-(2-pyrrolidin-2-yl-ethyl)-benzoate (Intermediate 35, 2.05 g), palladium acetate (0.282 g), cesium carbonate (3.26 g) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (1.557 g) in toluene (40 mL) was stirred and heated at 100° C. under nitrogen for one hour. After cooling, the mixture was diluted with ethyl acetate, washed with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30% to give methyl 7-(2,2-dimethylpropionylamino)-1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoline-6-carboxylate (0.826 g) as a pale yellow solid.

Workup

temperatureAfter cooling
washwashed with water
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo
customthe residue was purified by chromatography on silica
washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30%

Sources & evidence

ORD record: ord-e64dfdef5a6f460385b3dba91bb4f549
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187494B2

Reaction notes

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