Dimethylformamide → N-[2-(2-Chlorophenyl)-2-oxoethyl]-4-(phenylmethyl)-2-morpholinecarboxamide

HRID 2367527Notes

Reaction equation

HRID 2367527 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]1([CH2:13][N:14]2[CH2:19][CH2:18][O:17][CH:16]([C:20]([OH:22])=O)[CH2:15]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CN(C=O)C.C(N(CC)CC)C.[NH2:35][CH2:36][C:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[Cl:45])=[O:38]>C(Cl)Cl.O>[Cl:45][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=1[C:37](=[O:38])[CH2:36][NH:35][C:20]([CH:16]1[O:17][CH2:18][CH2:19][N:14]([CH2:13][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:15]1)=[O:22]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27763534-Benzylmorpholine-2-carboxylic acidHCID 30149362-Amino-1-(2-chlorophenyl)ethanone

Product 1

HCID 66990762N-[2-(2-Chlorophenyl)-2-oxoethyl]-4-(phenylmethyl)-2-morpholinecarboxamideYield 16.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Oxalyl chloride (0.765 mL, 8.73 mmol) was added to a suspension of 4-(phenylmethyl)-2-morpholinecarboxylic acid (1.288 g, 5.82 mmol) and DMF (0.090 mL, 1.165 mmol) in CH2Cl2 (80 mL) at 0° C. over 10 minutes. The reaction mixture was stirred at 25° C. for 2 h, and then concentrated. The residue was dissolved in CH2Cl2 (80 mL), then triethylamine (2.029 mL, 14.56 mmol) and 2-amino-1-(2-chlorophenyl)ethanone (1.2 g, 5.82 mmol) were added to the brown solution at 0° C. The mixture was stirred at 25° C. for 3 hours, and at this time, water (150 mL) was added. The mixture was extracted with EtOAc (3×100 mL), and the combined organics were dried with anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by silica gel chromatography using 50% EtOAc in petroleum ether to afford the title compound (350 mg) as a pale yellow solid. LC-MS (ES) m/z=373 [M+H]+.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
  3. stirringThe mixture was stirred at 25° C. for 3 hours
  4. extractionThe mixture was extracted with EtOAc (3×100 mL)
  5. dry with materialthe combined organics were dried with anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-7ec8b37daf3e4dbaa3b48140a3313441
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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