Dichloromethane → HCID 58577826, compound

HRID 473965Notes

Reaction equation

HRID 473965 reaction equation
ClCCl.C(=O)([O-])[O-].[K+].[K+].Br[C:11]1[CH:20]=[C:19]2[C:14]([C:15]([C:22]([OH:24])=[O:23])=[CH:16][C:17]([CH3:21])=[N:18]2)=[CH:13][CH:12]=1.[CH3:25][C:26]([CH3:48])([CH2:31][O:32][C:33]1[CH:38]=[CH:37][C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=1)[C:27]([O:29][CH3:30])=[O:28]>C(O)(C)C.O1CCOCC1>[CH3:30][O:29][C:27](=[O:28])[C:26]([CH3:25])([CH3:48])[CH2:31][O:32][C:33]1[N:34]=[CH:35][C:36]([C:11]2[CH:20]=[C:19]3[C:14]([C:15]([C:22]([OH:24])=[O:23])=[CH:16][C:17]([CH3:21])=[N:18]3)=[CH:13][CH:12]=2)=[CH:37][CH:38]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 162281747-Bromo-2-methylquinoline-4-carboxylic acidHCID 58577788HCID 58577788, compound

Product 1

HCID 58577826HCID 58577826, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Procedure

[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (40.8 mg, 0.05 mmol) and an aqueous solution of potassium carbonate (0.72 g, 4 mmol in 1.0 mL of water) were successively added to a solution of 7-bromo-2-methylquinoline-4-carboxylic acid B-14 (0.26 g, 1.00 mmol) and methyl 2,2-dimethyl-3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)propanoate A-7 (0.43 g, 1.50 mmol) in isopropanol (5.0 mL) and 1,4-dioxane (20 mL). The reaction was degassed several times under reduced pressure, placed under a nitrogen atmosphere and stirred at room temperature for 24 h. After quenching with a 1 N aqueous hydrogen chloride solution (2.0 mL), the mixture was filtered through a celite pad, washed with ethyl acetate (100 mL) and concentrated to dryness under reduced pressure. The residue was purified by flash column chromatography on silica gel (20:1 CH2Cl2:MeOH) to give 7-(6-(3-methoxy-2,2-dimethyl-3-oxopropoxy)pyridin-3-yl)-2-methylquinoline-4-carboxylic acid B-15 as a brown solid (0.32 g, Yield=82%). MS (ESI), [M+1]+ 395.

Workup

  1. customThe reaction was degassed several times under reduced pressure
  2. customAfter quenching with a 1 N aqueous hydrogen chloride solution (2.0 mL)
  3. filtrationthe mixture was filtered through a celite pad
  4. washwashed with ethyl acetate (100 mL)
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe residue was purified by flash column chromatography on silica gel (20:1 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-c9d9e9ff024e4a10ada100a0ad7dbc67
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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