Reacción #42354

Ecuación de reacción

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

methyl hydrogen isophthalate

diisopropylethylamine

HATU

→

title compound

Methyl 3-[({(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}amino)carbonyl]benzoate

Disolventes

DMF chloroform

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction is partitioned between ethyl acetate and water
2. 2
   LavadoThe organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine
3. 3
   Secadodried (sodium sulfate)
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   OtroPurification by flash column chromatography (silica, 8% methanol/chloroform)

Procedimiento

To methyl hydrogen isophthalate (1.0 g, 5.6 mmol) in DMF/chloroform (1:2, 15 mL) is added diisopropylethylamine (3.9 mL, 22 mmol), HATU (2.5 g, 6.7 mmol), then (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method of Example SP-272 (2.5 g, 6.1 mmol). The reaction is stirred 1 h at room temperature. The reaction is partitioned between ethyl acetate and water. The organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/chloroform) gives the title compound. ESI MS m/z 497.3 [M+H]+.

Fuente