Ethylmorpholine → 4-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid ethyl ester

HRID 1185590Notes

Reaction equation

HRID 1185590 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]([O:16][CH2:17][C:18]([OH:20])=O)[C:13]2[C:8](=[CH:9][C:10]([CH3:21])=[CH:11][CH:12]=2)[N:7]=1)=[O:5])[CH3:2].FC1C(O)=C(F)C(F)=C(F)C=1F.[N:34]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.C(N1CCOCC1)C>CN(C=O)C.C(Cl)Cl.C(Cl)CCl>[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]([O:16][CH2:17][C:18]([N:37]2[CH2:36][CH2:35][N:34]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38]2)=[O:20])[C:13]2[C:8](=[CH:9][C:10]([CH3:21])=[CH:11][CH:12]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 7525EthylmorpholineHCID 13041PentafluorophenolHCID 143452tert-Butyl piperazine-1-carboxylateHCID 686015834-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid ethyl ester

Product 1

HCID 685992624-[2-(4-tert-Butoxycarbonyl-piperazin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 990 mg 4-Carboxymethoxy-7-methyl-quinoline-2-carboxylic acid ethyl ester in 5 ml DMF were added 945 mg pentafluorophenol and 984 mg EDC. The mixture was stirred under exclusion of moisture until LCMS indicated complete conversion to the corresponding pentafluorophenolester. Tert-Butyl 1-piperazinecarboxylate (437 mg) was mixed with 0.8 ml N-ethylmorpholine and 10 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%) and saturated aqueous NaHCO3. The crude product obtained after evaporation of the solvent was purified by flash chromatography on silica eluting with ethyl acetate/heptane gradient. Yield: 988 mg.

Workup

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

Sources & evidence

ORD record
ord-c8862b118eaf42b9a8e3fcd32464dfa4
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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