Reaktion #42354

Reaktionsgleichung

(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

Lösungsmittel

DMF chloroform

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction is partitioned between ethyl acetate and water
2. 2
   WaschenThe organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine
3. 3
   Trocknendried (sodium sulfate)
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   SonstigePurification by flash column chromatography (silica, 8% methanol/chloroform)

Vorschrift

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]+.

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