Potassium Carbonate → HCID 58732756, compound

HRID 553006Notes

Reaction equation

HRID 553006 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:31][CH3:32])[C:9]([C@@H:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([C:21](=[O:29])[C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)[C@@H:13]([CH3:30])[CH2:12]2)=[O:10])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:39]([O:41][C:42](=[O:47])[CH2:43][CH2:44][CH2:45]Br)[CH3:40]>CN(C)C=O>[CH2:39]([O:41][C:42](=[O:47])[CH2:43][CH2:44][CH2:45][O:28][C:25]1[CH:24]=[CH:23][C:22]([C:21]([N:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C@@H:11]([C:9](=[O:10])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:31][CH3:32])[CH2:12][C@@H:13]2[CH3:30])=[O:29])=[CH:27][CH:26]=1)[CH3:40].[CH2:39]([O:41][C:42](=[O:47])[CH2:43][CH2:44][CH2:45][O:28][C:25]1[CH:24]=[CH:23][C:22]([C:21]([N:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C@H:11]([C:9](=[O:10])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:31][CH3:32])[CH2:12][C@@H:13]2[CH3:30])=[O:29])=[CH:27][CH:26]=1)[CH3:40]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 58732705HCID 58732705, compound

Product 2

HCID 58732756HCID 58732756, compoundYield 88%HCID 86608599HCID 86608599, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

(±)-trans-1-(4-Hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (585 mg, 1.30 mmol) was dissolved in dimethylformamide (20 mL). Potassium carbonate (1.5 g) was added, followed by ethyl-4-bromobutyrate (2.53 g, 1.9 mL, 13 mmol). The reaction was warmed to 90° C. and stirred under nitrogen overnight. Upon completion, the reaction was cooled to room temperature. The solvent layer was decanted and concentrated. The residue was dissolved in ethyl acetate. The residual solids in the reaction flask were washed with ethyl acetate and the washings combined with the filtrate ethyl acetate solution. The combined ethyl acetate layers were washed with water (3×) and brine, dried over sodium sulfate, filtered, and concentrated to afford the crude product. The crude material was a mixture of cis and trans isomers due to racemization under the alkylation conditions. The mixture was purified by silica gel chromatography (ethyl acetate/hexanes gradient) to afford pure (±)-trans-4-(4-{4-[(4-chloro-phenyl)-ethyl-carbamoyl]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid ethyl ester as a foam (88%) and pure (±)-cis-4-(4-{4-[(4-Chloro-phenyl)-ethyl-carbamoyl]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid ethyl ester. Data for the trans isomer: 1H-NMR (CDCl3) δ: 0.97 (d, 3H), 1.13 (t, 3H), 1.24 (t, 3H), 1.73 (ddd, 1H), 2.01-2.14 (m, 2H), 2.41-2.59 (m, 3H), 3.61-4.00 (m, 5H), 4.06-4.18 (m, 2H), 5.01-5.14 (m, 1H), 6.44 (d, 1H), 6.68-6.84 (m, 4H), 6.89 (dd, 1H), 7.16-7.27 (m, 2H), 7.42-7.51 (m, 4H). MS m/z: 563 (M+1).

Workup

  1. temperatureUpon completion, the reaction was cooled to room temperature
  2. customThe solvent layer was decanted
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washThe residual solids in the reaction flask were washed with ethyl acetate
  6. washThe combined ethyl acetate layers were washed with water (3×) and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford the crude product
  11. additiona mixture of cis and trans isomers due to racemization under the alkylation conditions
  12. customThe mixture was purified by silica gel chromatography (ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-e32959d9a0e04bcc930111282af11f8b
Source dataset
uspto-grants-2011_05
Patent number
US07951950B2

Reaction notes

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