Ethanol → HCID 86696587, compound

HRID 1854876Notes

Reaction equation

HRID 1854876 reaction equation
Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].C(O)C.C(=O)([O-])[O-].[Na+].[Na+].[O:30]=[C:31]1[CH:40]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:39][C:38]2[C:33](=[CH:34][C:35](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:37]=2)[NH:32]1>C1(C)C=CC=CC=1.C(Cl)Cl.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:44]([O:43][C:42]([NH:41][CH:40]1[CH2:39][C:38]2[C:33](=[CH:34][C:35]([C:2]3[CH:3]=[CH:4][N:5]4[C:10]([C:11]=3[CH3:12])=[C:9]([CH:13]3[CH2:15][CH2:14]3)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]4=[O:20])=[CH:36][CH:37]=2)[NH:32][C:31]1=[O:30])=[O:48])([CH3:47])([CH3:45])[CH3:46]

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 66980368HCID 66980368, compoundHCID 86696543Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-quinolizine-3-carboxylate

Product 1

HCID 86696587HCID 86696587, compoundYield 55.4%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (45 mg, 0.15 mmol) was dissolved in toluene (330 μL), ethanol (96%) (243 μL) and 2M aqueous sodium carbonate solution (231 μL, 0.463 mmol). tert-Butyl 2-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-3-ylcarbamate (78 mg, 0.20 mmol) was added and the mixture was degassed with argon. 1,1′-Bis(diphenylphosphino)-ferrocene palladium(II) dichloride (11.3 mg, 0.015 mmol) was added and the mixture was heated at 80° C. under an argon atmosphere for 16 h. After cooling, the mixture was diluted with CH2Cl2 (3 mL) and water (3 mL) and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3×2 mL). The combined organic layers were concentrated and the yellow crude product was purified with flash silica column chromatography (heptane/ethyl acetate) (1:0 to 0:1) to afford the title compound as a yellow solid (43 mg, 53%). ESI-MS m/z: 518 (M+H)+.

Workup

  1. customthe mixture was degassed with argon
  2. temperatureAfter cooling
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with CH2Cl2 (3×2 mL)
  5. concentrationThe combined organic layers were concentrated
  6. customthe yellow crude product was purified with flash silica column chromatography (heptane/ethyl acetate) (1:0 to 0:1)

Sources & evidence

ORD record
ord-300c0d1bb31246f38c8a96f2ed0d1d6e
Source dataset
uspto-grants-2015_02
Patent number
US08962842B2

Reaction notes

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