Oxalyl chloride → (+/-)-trans-1-(4-Methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid benzyl-ethyl-amide

HRID 553004Notes

Reaction equation

HRID 553004 reaction equation
[CH3:1][O:2][C:3]1[CH:24]=[CH:23][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][CH:10]2[CH3:22])=[O:8])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[CH2:40]([NH:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH3:41]>C(Cl)Cl.CN(C)C=O.C(OCC)(=O)C>[CH2:43]([N:42]([CH2:40][CH3:41])[C:19]([C@@H:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:9]([C:7](=[O:8])[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:24][CH:23]=2)[C@@H:10]([CH3:22])[CH2:11]1)=[O:20])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 84352N-EthylbenzylamineHCID 671658371-(4-Methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid

Product 1

HCID 58732730(+/-)-trans-1-(4-Methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid benzyl-ethyl-amideYield 34%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-(4-Methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (2.00 g, 6.15 mmol) was suspended in methylene chloride (50 mL). One drop of dimethylformamide was added, followed by oxalyl chloride (1.56 g, 1.07 mL, 12.3 mmol). The suspension became homogeneous on stirring. After 2 hours, the yellow solution was concentrated under reduced pressure and azeotroped with toluene. To a solution of the resulting acid chloride (120 mg, 349 mmol) in methylene chloride (1 mL) was added diisopropylethylamine (451 uL, 0.349 mmol), followed by ethyl-benzyl-amine (71 mg, 77 uL, 0.523 mmol). The mixture was shaken overnight at room temperature. Upon completion, the reaction was diluted with ethyl acetate, washed with saturated sodium bicarbonate (aqueous) and brine, dried over sodium sulfate, filtered and concentrated to afford the crude amide. Purification by silica gel chromatography (elution with a hexane/ethyl acetate gradient) afforded pure (±)-trans-1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid benzyl-ethyl-amide (53 mg, 34%). 1H-NMR (CDCl3) δ: 0.98 (d, 3H), 1.13 (t, 3H), 1.74 (ddd, 1H), 2.52 (ddd, 1H), 3.62-3.92 (m, 8H), 5.03-5.13 (m, 1H), 6.44 (d, 1H), 6.72-6.84 (m, 4H), 6.86-6.92 (m, 1H), 7.19-7.23 (m, 2H), 7.43-7.54 (m, 4H). MS m/z: 443 (M+1).

Workup

  1. concentrationthe yellow solution was concentrated under reduced pressure
  2. customazeotroped with toluene
  3. stirringThe mixture was shaken overnight at room temperature
  4. washwashed with saturated sodium bicarbonate (aqueous) and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude amide
  9. customPurification by silica gel chromatography (
  10. washelution with a hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-1e0e7ebb1717495c97df577861581b3f
Source dataset
uspto-grants-2011_05
Patent number
US07951950B2

Reaction notes

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