Oxalyl chloride → HCID 67165232, compound

HRID 553013Notes

Reaction equation

HRID 553013 reaction equation
[CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]([C:7]([N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]([C:19](O)=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[Cl:39][C:40]1[CH:48]=[CH:47][C:43]([NH:44][CH2:45][CH3:46])=[CH:42][CH:41]=1>C(Cl)Cl.CN(C)C=O.C(OCC)(=O)C>[Cl:39][C:40]1[CH:48]=[CH:47][C:43]([N:44]([CH2:45][CH3:46])[C:19]([CH:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:9]([C:7](=[O:8])[C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:23][CH:22]=3)[CH2:10][CH2:11]2)=[O:20])=[CH:42][CH:41]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 5878414-chloro-N-ethylanilineHCID 67165918HCID 67165918, compound

Product 1

HCID 67165232HCID 67165232, compoundYield 29.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(4-Methoxy-benzoyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (approx. 1.47 mmol) was suspended in methylene chloride (10 mL) to which one drop of dimethylformamide was added. Oxalyl chloride (375 mg, 275 uL, 2.95 mmol) was added. Vigorous bubbling ensued, followed by dissolution of the starting material. After stirring for 4 hours at room temperature, the yellow solution was concentrated and azeotroped with toluene to remove excess oxalyl chloride. The resulting acid chloride solution was dissolved in methylene chloride (10 mL). Diisopropylethylamine (569 mg, 768 uL, 4.41 mmol) was added, followed by 4-chloro-N-ethylaniline (457 mg, 2.93 mmol). The mixture was stirred at room temperature overnight. The reaction was poured into ethyl acetate and washed with water and brine. The combined organics were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (ethyl acetate/hexanes gradient) to afford (±)-1-(4-methoxy-benzoyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (193 mg) as a foam. 1H-NMR (CDCl3) δ: 1.17 (t, 3H), 2.06-2.26 (m, 2H), 3.57-3.70 (m, 2H), 3.73-3.87 (m, 5H), 4.02 (dd, 1H), 6.52 (d, 1H), 6.66-6.74 (m, 2H), 6.84 (ddd, 1H), 6.93-7.06 (m, 2H), 7.17-7.24 (m, 2H), 7.37-7.43 (m, 2H). MS m/z: 449 (M+1).

Workup

  1. additionwas added
  2. customVigorous bubbling
  3. dissolutionfollowed by dissolution of the starting material
  4. concentrationthe yellow solution was concentrated
  5. customazeotroped with toluene
  6. customto remove excess oxalyl chloride
  7. dissolutionThe resulting acid chloride solution was dissolved in methylene chloride (10 mL)
  8. stirringThe mixture was stirred at room temperature overnight
  9. washwashed with water and brine
  10. dry with materialThe combined organics were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude residue was purified by silica gel chromatography (ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-5e559d037304404c85d2868114cb6c6a
Source dataset
uspto-grants-2011_05
Patent number
US07951950B2

Reaction notes

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