Aniline → 3-Hydroxymethylheptanoic acid phenylamide

HRID 273193Notes

Reaction equation

HRID 273193 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.[CH2:12]([CH:16]1[CH2:20][O:19][C:18](=[O:21])[CH2:17]1)[CH2:13][CH2:14][CH3:15]>C1(C)C=CC=CC=1>[C:2]1([NH:1][C:18](=[O:21])[CH2:17][CH:16]([CH2:20][OH:19])[CH2:12][CH2:13][CH2:14][CH3:15])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6115AnilineHCID 127357064-Butyloxolan-2-oneHCID 16682925Trimethylaluminum

Product 1

HCID 693120333-Hydroxymethylheptanoic acid phenylamideYield 70.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of aniline (0.36 mL, 4.0 mmol) in toluene (10 mL) was added trimethylaluminum in toluene (2M, 2.5 mL, 5 mmol). After 20 min, a solution of (+/−)-4-butyldihydrofuran-2-one (0.4 g, 4 mmol) in toluene (1 mL) was added and the reaction mixture was refluxed for 3 h. The reaction was cooled to 0° C. and carefully quenched with 1 M HCl (15 mL), and then extracted with dichloromethane (3×15 mL). The combined extractions were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (silica gel, ethyl acetate/hexanes 3:2) to afford 3-hydroxymethylheptanoic acid phenylamide as a white solid (0.66 g, 70%). MS(ES) m/e 236 [M+H]+.

Workup

  1. temperaturethe reaction mixture was refluxed for 3 h
  2. customcarefully quenched with 1 M HCl (15 mL)
  3. extractionextracted with dichloromethane (3×15 mL)
  4. extractionThe combined extractions
  5. dry with materialwere dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography (silica gel, ethyl acetate/hexanes 3:2)

Sources & evidence

ORD record
ord-ca61eec070ef4dee9b2a973eed823848
Source dataset
uspto-grants-2008_11
Patent number
US07456211B2

Reaction notes

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