Reacción #810592

Ecuación de reacción

(7R,8R,9R)-10-acetyl-7-hydroxy-2-methyl-9-phenyl-8-pivaloyloxy-7.8.9.10-tetrahydroimidazo[1.2-h][1.7]naphthyridine

methoxyethyl triflate

sodium hydride

→

title compound

(7R,8R,9R)-10-Acetyl-7-(2-methoxyethoxy)-2-methyl-9-phenyl-8-pivaloyloxy-7.8.9.10-tetrahydroimidazo[1.2-h][1.7]naphthyridine

Disolventes

dichloromethane

N-methyl-pyrrolidinone

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction is quenched
2. 2
   workup.ADDITIONby adding of saturated aqueous ammonium chloride solution
3. 3
   ExtracciónSubsequently the mixture is extracted twice with dichloromethane
4. 4
   LavadoThe combined organic layers are washed with brine
5. 5
   Secadodried over sodium sulphate
6. 6
   Otroevaporated in vacuo
7. 7
   OtroThe crude product is purified by column chromatography (ethyl acetate/cyclohexane/triethylamine: 5/4/1)

Procedimiento

To a of −30° C. cooled solution of 7.40 g (17.6 mmol) (7R,8R,9R)-10-acetyl-7-hydroxy-2-methyl-9-phenyl-8-pivaloyloxy-7.8.9.10-tetrahydroimidazo[1.2-h][1.7]naphthyridine in dichloromethane (25 ml) and N-methyl-pyrrolidinone (25 ml) is added 4.00 g (19.3 mmol) methoxyethyl triflate and 1.40 g (35.2 mmol) sodium hydride and it is stirred for further 2 h at this temperature. The reaction is quenched by adding of saturated aqueous ammonium chloride solution. Subsequently the mixture is extracted twice with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulphate and evaporated in vacuo. The crude product is purified by column chromatography (ethyl acetate/cyclohexane/triethylamine: 5/4/1) to give 7.50 g (15.63 mmol/89%) of the title compound as a yellow amorphous solid. 1H-NMR (200 MHz, [D6] DMSO): δ=1.19(s, 9H), 2.15(s, 3H), 2.38(s, 3H), 3.27(s, 3H), 3.45–3.57(m, 2H), 3.83–3.93(m, 2H), 4.60(d, 1H), 5.31(t, 1H), 5.79(d, 1H), 6.94 (s, 1H), 7.20(s, 5H); 7.74(s, 1H), 8.43(d, 1H).

Fuente