Reaction #508690

Reaction equation

triethylamine

2-amino-4-methoxymethoxymethyl-thiophene-3-sulfonic acid amide

3,3-diethoxy-acrylic acid ethyl ester

→

(7-methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-acetic acid ethyl ester

Yield 52.2%

Solvents

ethyl acetate

N,N-dimethylformamide

Conditions

Workup

1. 1
   workup.ADDITIONwas added to the mixture
2. 2
   TemperatureIt was then cooled to 25° C.
3. 3
   Washwashed with 1.0 M aqueous hydrochloric acid solution (10 mL)
4. 4
   DryingThe organic layer was dried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-80% ethyl acetate in hexanes)

Procedure

To a solution of 2-amino-4-methoxymethoxymethyl-thiophene-3-sulfonic acid amide (0.76 g, 3.01 mmol) in N,N-dimethylformamide (10 mL) at 25° C. was added 3,3-diethoxy-acrylic acid ethyl ester (0.68 g, 3.61 mmol). The reaction was stirred at 70° C. for 5 h before triethylamine (1.68 mL, 12.04 mmol) was added to the mixture. The reaction was stirred at 70° C. overnight. It was then cooled to 25° C., diluted with ethyl acetate (10 mL) and washed with 1.0 M aqueous hydrochloric acid solution (10 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-80% ethyl acetate in hexanes) to afford the desired product, (7-methoxymethoxymethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-acetic acid ethyl ester (0.55 g, 1.57 mmol, 52%), as a brown oil. 1H NMR (400 MHz, CDCl3) δ: 1.32 (3H, t, J=7.2 Hz), 3.42 (3H, s), 3.68 (2H, s), 4.26 (2H, q, J=7.2 Hz), 4.76 (2H, s), 4.80 (2H, s), 7.00 (1H, s), 8.00 (1H, s).

Source