Tetrahydrofuran → N-(2-Chloro-3-ethoxy-5-formyl-phenyl)-acetamide

HRID 1990863Notes

Reaction equation

HRID 1990863 reaction equation
CO[C:3](=[O:15])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH3:12])[C:7]([Cl:13])=[C:6]([NH2:14])[CH:5]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1C[O:25][CH2:24][CH2:23]1>O=[Mn]=O>[Cl:13][C:7]1[C:8]([O:10][CH2:11][CH3:12])=[CH:9][C:4]([CH:3]=[O:15])=[CH:5][C:6]=1[NH:14][C:24](=[O:25])[CH3:23]

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 21226445Aluminium lithium hydrideHCID 686990463-Amino-4-chloro-5-ethoxy-benzoic acid methyl ester

Product 1

HCID 58706332N-(2-Chloro-3-ethoxy-5-formyl-phenyl)-acetamideYield 45%

Reagents, catalysts & solvents 1

HCID 14801Manganese dioxideCatalyst

Procedure

To a solution of 3-amino-4-chloro-5-ethoxy-benzoic acid methyl ester (1.8 g, 6.63 mmol, 1.0 equiv) in anhydrous THF (50 mL) was added lithium aluminium hydride (0.50 g, 13.25 mmol, 2.0 equiv) and the reaction mixture stirred at rt for 4 h. The crude reaction mixture was filtered, the filtrate extracted with diethyl ether (3×50 mL) and the combined organic phases dried over MgSO4 providing 1.58 g (100%) of the benzyl alcohol. The crude reaction product (0.13 g, 0.53 mmol, 1.0 equiv) was dissolved in THF (20 mL) and activated MnO2 (0.46 g, 5.34 mmol, 10.0 equiv) was added. After stirring at rt for 1 h, the reaction mixture was filtered and the solvent removed by evaporation under reduced pressure. A conc. solution of sodium chloride (100 mL) was added, the mixture extracted with ethyl acetate (3×100 mL) and the combined organic phases dried over MgSO4. Purification of the crude material with column chromatography on silica eluting with heptane/ethyl acetate (2:1) provided 0.058 g (45%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.49 (t, J=7.0 Hz, 3H), 2.29 (s, 3H), 4.19 (q, J=7.0 Hz, 2H), 7.22 (d, J=1.6 Hz, 1H), 7.78 (br s, 1H), 8.56 (br s, 1H), 9.94 (br s, 1H). MS (ISP): 242.1 [M+H]+.

Workup

  1. customThe crude reaction mixture
  2. filtrationwas filtered
  3. extractionthe filtrate extracted with diethyl ether (3×50 mL)
  4. dry with materialthe combined organic phases dried over MgSO4 providing 1.58 g (100%) of the benzyl alcohol
  5. stirringAfter stirring at rt for 1 h
  6. filtrationthe reaction mixture was filtered
  7. customthe solvent removed by evaporation under reduced pressure
  8. additionA conc. solution of sodium chloride (100 mL) was added
  9. extractionthe mixture extracted with ethyl acetate (3×100 mL)
  10. dry with materialthe combined organic phases dried over MgSO4
  11. customPurification of the crude material with column chromatography on silica eluting with heptane/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-75161dcb68c84851b6d9e60dd57188ae
Source dataset
uspto-grants-2010_01
Patent number
US07645753B2

Reaction notes

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