Methanamine, N-methoxy-, hydrochloride (1:1) → (e)-3-(4-Fluorophenyl)-n-methoxy-n,2-dimethylacrylamide

HRID 514656Notes

Reaction equation

HRID 514656 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[C:9](\[CH3:13])/[C:10](O)=[O:11])=[CH:4][CH:3]=1.Cl.[CH3:15][NH:16][O:17][CH3:18].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[C:9](\[CH3:13])/[C:10]([N:16]([O:17][CH3:18])[CH3:15])=[O:11])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 53886943-(4-Fluorophenyl)-2-methylacrylic acid

Product 1

HCID 87521933(e)-3-(4-Fluorophenyl)-n-methoxy-n,2-dimethylacrylamideYield 84.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of Example 1B (16.1 g, 89.4 mmol), N,O-dimethylhydroxylamine hydrochloride (9.15 g, 93.9 mmol), 1-hydroxybenzotriazole hydrate (12.7 g, 93.9 mmol), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (17.9 g, 93.9 mmol), and diisopropylethyl amine (47.4 g, 370 mmol) was stirred in DMF (400 mL) at ambient temperature overnight. The solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution, 1N HCl, water, brine, dried over Na2SO4, and evaporated in vacuo. The resulting material was chromatographed (SiO2, 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) to yield the title compound (16.89 g, 58% yield) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ ppm 7.33 (dd, J=8.82, 5.43 Hz, 2H), 7.00-7.14 (m, 2H), 6.79 (s, 1H), 3.70 (s, 3H), 3.29 (s, 3H), 2.11 (s, 3H). MS (DCI+) 224 (M+H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with saturated sodium bicarbonate solution, 1N HCl, water, brine
  3. dry with materialdried over Na2SO4
  4. customevaporated in vacuo
  5. customThe resulting material was chromatographed (SiO2, 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4759a69e6a0b433795e04f1749462b65
Source dataset
uspto-grants-2015_08
Patent number
US09108905B2

Reaction notes

Loading…