Ethylmorpholine → 4-[2-(3,3-Difluoro-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid methyl ester

HRID 1185579Notes

Reaction equation

HRID 1185579 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH2:16][C:17]([OH:19])=O)[C:12]2[C:7](=[CH:8][C:9]([CH3:20])=[CH:10][CH:11]=2)[N:6]=1)=[O:4].FC1C(O)=C(F)C(F)=C(F)C=1F.Cl.[F:34][C:35]1([F:40])[CH2:39][CH2:38][NH:37][CH2:36]1.C(N1CCOCC1)C>CN(C=O)C.C(Cl)Cl.C(Cl)CCl>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH2:16][C:17]([N:37]2[CH2:38][CH2:39][C:35]([F:40])([F:34])[CH2:36]2)=[O:19])[C:12]2[C:7](=[CH:8][C:9]([CH3:20])=[CH:10][CH:11]=2)[N:6]=1)=[O:4]

Participants

8

Reactant 4

HCID 7525EthylmorpholineHCID 13041PentafluorophenolHCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 685989324-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid methyl ester

Product 1

HCID 685982264-[2-(3,3-Difluoro-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 900 mg 4-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid methyl ester in 5 ml DMF were added 902 mg pentafluorophenol and 940 mg EDC. The mixture was stirred under exclusion of moisture until LCMS indicated complete conversion to the corresponding pentafluorophenolester. 3,3-Difluoropyrrolidine hydrochloride (455 mg) was mixed with 1.2 ml N-ethylmorpholine and 5 ml DMF and this mixture added dropwise to the solution of the pentafluorophenolester. After 12 h the reaction mixture was diluted with DCM and washed with aqueous LiCl (4%), saturated aqueous NaHCO3 and brine. The crude product obtained after evaporation of the solvent was purified by flash chromatography on silica eluting with ethyl acetate/heptane gradient. Yield: 815 mg.

Workup

  1. additionthis mixture added dropwise to the solution of the pentafluorophenolester
  2. washwashed with aqueous LiCl (4%), saturated aqueous NaHCO3 and brine

Sources & evidence

ORD record
ord-195c1b96375348c68f7abfb30b9918bd
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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