Triethylamine → N-Methoxy-N-methyl-(2S)-(3,4-dichlorophenyl)-4-pentenamide

HRID 1737435Notes

Reaction equation

HRID 1737435 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:13][CH:14]=[CH2:15])[C:10](O)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].O.ON1C2C=CC=CC=2N=N1.Cl.[CH3:28][NH:29][O:30][CH3:31].C(N(CC)CC)C>C(Cl)Cl>[CH3:31][O:30][N:29]([CH3:28])[C:10](=[O:11])[C@H:9]([C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1)[CH2:13][CH:14]=[CH2:15]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 15261879(S)-2-(3,4-dichlorophenyl)pent-4-enoic acid

Product 1

HCID 18392767N-Methoxy-N-methyl-(2S)-(3,4-dichlorophenyl)-4-pentenamideYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
22 °C

Procedure

A mixture of 306 mg (1.25 mmol) of (2S)-(3,4-dichlorophenyl)-4-pentenoic acid (prepared according to the procedure of Hale, J. J.; Finke, P. E.; MacCoss, M. Bioorganic & Medicinal Chemistry Letters 1993,3, 319-322) and 202 mg (1.50 mmol) of 1-hydroxybenzotriazole hydrate in 10 mL of methylene chloride was cooled to 0° C. and treated with 287 mg (1.50 mmol) of 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide. The cooling bath was removed and after 45 min. a solution of 365 mg (3.75 mmol) of N,O-dimethyl-hydroxylamine hydrochloride and 522 μl (3.75 mmol) of triethylamine in 10 mL of methylene chloride was added via cannula. The mixture was then stirred at 22° C. for 4 hours and then quenched with 10 mL of water and diluted with 8 mL of methylene chloride. The layers were separated and the aqueous layer was extracted with methylene chloride (2×10 mL). The combined organic layers were washed with 10 mL of brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography on 75 g of silica gel using 1:9 v/v ethyl acetate/hexane as the eluant afforded 319 mg (89%) of the title compound as a clear oil. 1H NMR (400 MHz, CDCl3) δ 2.40 (pentet, 1H), 2.75 (pentet, 1H), 3.13 (s, 3H), 3.52 (s, 3H), 3.99-4.01 (m, 1H), 4.96-5.05 (m, 2H), 5.63-5.70 (m, 1H), 7.15 (dd, 1H), 7.35 (d, 1H), 7.41 (d, 1H). Mass Spectrum (FAB): m/z 290 (M+H, 37Cl+35Cl isotope, 50%), 288 (M+H, 37Cl+37Cl isotope, 100%).

Workup

  1. customprepared
  2. additionwas added via cannula
  3. customquenched with 10 mL of water
  4. additiondiluted with 8 mL of methylene chloride
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with methylene chloride (2×10 mL)
  7. washThe combined organic layers were washed with 10 mL of brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a8cb5da7f44e48e2a447238781ad717a
Source dataset
uspto-grants-1999_10
Patent number
US05962462

Reaction notes

Loading…