Sodium Carbonate → (S)-methyl 5-cyclobutoxy-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoline-1 (2H)-carboxylate

HRID 1051667Notes

Reaction equation

HRID 1051667 reaction equation
CC1(C)OB([C:7]2[CH:8]=[N:9][N:10](C(OC(C)(C)C)=O)[CH:11]=2)OC1(C)C.Br[C:23]1[C:24]([O:38][CH:39]2[CH2:42][CH2:41][CH2:40]2)=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]([C:33]([O:35][CH3:36])=[O:34])[C@@H:28]([CH3:37])[CH2:27][CH2:26]2.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH:39]1([O:38][C:24]2[C:23]([C:7]3[CH:11]=[N:10][NH:9][CH:8]=3)=[CH:32][CH:31]=[C:30]3[C:25]=2[CH2:26][CH2:27][C@H:28]([CH3:37])[N:29]3[C:33]([O:35][CH3:36])=[O:34])[CH2:40][CH2:41][CH2:42]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 118075694(S)-methyl 6-bromo-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118075439(S)-methyl 5-cyclobutoxy-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoline-1 (2H)-carboxylateYield 68.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

A 100-mL round-bottom flask was charged with tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (250 mg, 0.85 mmol), (S)-methyl 6-bromo-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (317 mg, 0.89 mmol), sodium carbonate (150 mg, 1.42 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (58 mg, 0.18 mmol), 1,4-dioxane (10 mL), and water (2 mL). The resulting mixture stirred overnight at 100° C. in an oil bath. After cooling to room temperature, the reaction mixture was poured into 10 mL of water and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×10 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 5:1, ethyl acetate/petroleum ether) to afford (S)-methyl 5-cyclobutoxy-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (200 mg, 52%) as yellow oil. MS (ESI, pos. ion) m/z 342 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified via column chromatography on silica gel (eluting with 5:1, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-89467246219f4fc9ae3542ed92f7e3e3
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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