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

A solution of isopropylmagnesium chloride (2.0 M in THF, 59.1 mL, 118 mmol) was added dropwise via addition funnel to a mixture of Example 1A (5.47 g, 26.3 mmol) and N,O-dimethylhydroxylamine hydrochloride (5.12 g, 52.5 mmol) in THF (100 mL) at 0° C. Upon complete addition, the reaction was allowed to proceed 2 hr at 0° C. The reaction was quenched by slow addition of saturated aq NH4Cl solution (70 mL). The mixture was stirred 60 min, then partitioned between EtOAc (50 mL) and H2O (100 mL). The separated aqueous phase was extracted with EtOAc, and the combined organic layer was washed with 1 N aq HCl and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (Analogix® Intelliflash 280; SF65-400 g column; 20% to 60% EtOAc/hexanes; 0-40 min) to give the title compound (5.06 g, 22.7 mmol, 86% yield) as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.50-7.40 (m, 2H), 7.29-7.18 (m, 2H), 6.72 (s, 1H), 3.65 (s, 3H), 3.19 (s, 3H), 2.01 (d, J=1.5 Hz, 3H). MS (DCI+) 224 (M+H).

1. additionUpon complete addition
2. customThe reaction was quenched by slow addition of saturated aq NH4Cl solution (70 mL)
3. custompartitioned between EtOAc (50 mL) and H2O (100 mL)
4. extractionThe separated aqueous phase was extracted with EtOAc
5. washthe combined organic layer was washed with 1 N aq HCl and brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by chromatography on silica gel (Analogix® Intelliflash 280; SF65-400 g column; 20% to 60% EtOAc/hexanes; 0-40 min)

ORD-Eintrag

ord-6fbf963d89424837abae7219af2347fa

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09108905B2