Ethanol → HCID 86696584, compound

HRID 1478314Notes

Reaction equation

HRID 1478314 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+].[F:30][C:31]1[CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH:43]=[CH:42][C:32]=1[CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38]>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:37]([O:36][C:35]([NH:34][CH2:33][C:32]1[CH:42]=[CH:43][C:44]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]3=[O:20])=[CH:45][C:31]=1[F:30])=[O:41])([CH3:40])([CH3:38])[CH3:39]

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 669802924-(n-Boc-aminomethyl)-3-fluorobenzeneboronic acid pinacol esterHCID 86696543Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-quinolizine-3-carboxylate

Product 1

HCID 86696584HCID 86696584, compoundYield 32%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
90 °C

Procedure

Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (46 mg, 0.158 mmol) was dissolved in toluene (500 μL), ethanol (96%) (237 μL) and aqueous sodium carbonate 2M (237 μL, 0.473 mmol). tert-Butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (97 mg, 0.21 mmol) was added. The mixture was degassed with argon and 1,1′-bis(diphenylphosphino)-ferrocene palladium(II) dichloride (11.5 mg, 0.016 mmol) was added. The mixture was heated at 90° C. for 4 h. After cooling, the mixture was diluted with DCM (3 mL) and water (3 mL). The layers were separated and the aqueous layer was extracted with DCM (3×2 mL). The organic layer was concentrated in vacuum. The crude product was purified with flash silica column chromatography (heptane:ethyl acetate) (1:1 to 1:2) to afford the title compound as a yellow solid (24 mg, 32%).

Workup

  1. additionwas added
  2. temperatureAfter cooling
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (3×2 mL)
  5. concentrationThe organic layer was concentrated in vacuum
  6. customThe crude product was purified with flash silica column chromatography (heptane:ethyl acetate) (1:1 to 1:2)

Sources & evidence

ORD record
ord-2f283a3422e7454d92e35ce5dc2c028d
Source dataset
uspto-grants-2016_08
Patent number
US09403818B2

Reaction notes

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