Triethylamine → Methyl [(4-phenyl)-5-(3,4-dichlorophenyl)oxazole] 2-butanoate

HRID 1057794Notes

Reaction equation

HRID 1057794 reaction equation
C[O:2][C:3]([CH2:5][CH2:6][CH2:7]CC(Cl)=O)=[O:4].[CH2:12]([N:14](CC)CC)[CH3:13].[Cl:19][C:20]1[CH:21]=[C:22]([CH:27]([OH:36])[C:28]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=O)[CH:23]=[CH:24][C:25]=1[Cl:26].C([O-])(=O)C.[NH4+]>C(Cl)Cl.C(O)(=O)C>[CH3:13][C:12]1[O:36][C:27]([C:22]2[CH:23]=[CH:24][C:25]([Cl:26])=[C:20]([Cl:19])[CH:21]=2)=[C:28]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:14]=1.[CH3:7][CH2:6][CH2:5][C:3]([OH:4])=[O:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 517165Ammonium AcetateHCID 520737Methyl 6-chloro-6-oxohexanoateHCID 225052602-(3,4-Dichlorophenyl)-2-hydroxy-1(phenyl)ethanone

Product 1

HCID 131723428Methyl [(4-phenyl)-5-(3,4-dichlorophenyl)oxazole] 2-butanoateYield 42,287.199%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

5-(Methoxycarbonyl)pentanoyl chloride (2.82 g, 0.017 mol) and triethylamine (3.47 g, 0.034 mol) were added to a solution of 2-(3,4-dichlorophenyl)-2-hydroxy-1-[phenyl]ethanone (Step 1) (4.77 g, 0.017 mmol) in 40 mL of methylene chloride. The resulting mixture was stirred overnight at room temperature. The reaction mixture was diluted with 100 mL of methylene chloride. The organic solution was washed with water (1×100 mL), saturated brine (1×100 mL), dried over magnesium sulfate, filtered and concentrated. The concentrated residue was dried under high vacuum, then ammonium acetate (4.6 g, 0.06 mol) and 30 mL of acetic acid were added. The reaction mixture was heated at 100° C. for 2.5 h. The reaction mixture was cooled to room temperature, and the excess acetic acid was removed under vacuum. The resulting residue was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was separated, washed with saturated aqueous sodium bicarbonate (2×100 mL), saturated brine (1×100 mL), dried over magnesium sulfate, filtered and concentrated. The concentrated residue was purified by flash chromatography on silica gel (eluting with 1:9 ethyl acetate:hexane) to give 2.82 g (42.6%) of methyl [(4-phenyl)-5-(3,4-dichlorophenyl)oxazole]-2-butanoate as a yellow oil: HRMS calcd. for C20H17N1O3Cl2 390.0664. Found 390.0648.

Workup

  1. washThe organic solution was washed with water (1×100 mL), saturated brine (1×100 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe concentrated residue was dried under high vacuum
  6. temperatureThe reaction mixture was heated at 100° C. for 2.5 h
  7. temperatureThe reaction mixture was cooled to room temperature
  8. customthe excess acetic acid was removed under vacuum
  9. customThe resulting residue was partitioned between water (100 mL) and ethyl acetate (200 mL)
  10. customThe organic layer was separated
  11. washwashed with saturated aqueous sodium bicarbonate (2×100 mL), saturated brine (1×100 mL)
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe concentrated residue was purified by flash chromatography on silica gel (eluting with 1:9 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-970b4e6b1a594c6793cc244ef66664fe
Source dataset
uspto-grants-2003_02
Patent number
US06515014B2

Reaction notes

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