Potassium Carbonate → 1-[2-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-ethyl]-cyclobutanecarboxylic acid ethyl ester

HRID 1786057Notes

Reaction equation

HRID 1786057 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C@H:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]([C:22](=[O:30])[C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[C@@H:14]([CH3:31])[CH2:13]2)[C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:38]([O:40][C:41]([C:43]1([CH2:47][CH2:48]Br)[CH2:46][CH2:45][CH2:44]1)=[O:42])[CH3:39]>CN(C=O)C>[CH2:38]([O:40][C:41]([C:43]1([CH2:47][CH2:48][O:29][C:26]2[CH:25]=[CH:24][C:23]([C:22]([N:15]3[C:16]4[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH:12]([N:8]([C:9](=[O:11])[CH3:10])[C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[CH2:13][CH:14]3[CH3:31])=[O:30])=[CH:28][CH:27]=2)[CH2:46][CH2:45][CH2:44]1)=[O:42])[CH3:39]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 58859774N-(4-chlorophenyl)-N-[(2S,4R)-1-(4-hydroxybenzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]acetamideHCID 671109491-(2-Bromo-ethyl)-cyclobutanecarboxylic acid ethyl ester

Product 1

HCID 689219411-[2-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-ethyl]-cyclobutanecarboxylic acid ethyl esterYield 67.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.17 g, 0.39 mmol) was dissolved in 5 ml DMF at room temperature and K2CO3 (0.323 g, 2.34 mmol) was added. 1-(2-Bromo-ethyl)-cyclobutanecarboxylic acid ethyl ester (0.184 g, 0.78 mmol) prepared according to the procedure from Tetrahedron 1994, 50(32), 9825-30 was added and the reaction was allowed to heat to 80° C. overnight. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water, then extracted three times with ethyl acetate, dried over MgSO4, filtered and concentrated down. The crude residue was purified by silica gel chromatography (50% EtOAc/50% Hexane) to afford the 1-[2-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-ethyl]-cyclobutanecarboxylic acid ethyl ester (0.155 g, 67%).

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. extractionextracted three times with ethyl acetate
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated down
  8. customThe crude residue was purified by silica gel chromatography (50% EtOAc/50% Hexane)

Sources & evidence

ORD record
ord-d48e91603a944558b4a6ae793cffb568
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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