Reaktion #42587

Reaktionsgleichung

hydrochloric acid

triphosgene

diisopropylethylamine

dihydrochloride

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

amino sulfone

tert-butyl 4-[(methylsulfonyl)methyl]piperidine-1-carboxylate

→

title compound

Ausbeute 7.2%

N-{(1S,2R) -1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)methyl]piperidine-1-carboxamide

Ausbeute 7.2%

Lösungsmittel

diethyl ether

methylene chloride

methylene chloride

methylene chloride

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was warmed until the solution
2. 2
   Waschenwashed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and saturated sodium chloride
3. 3
   Trocknendried (magnesium sulfate)
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   SonstigePurification by flash column chromatography (silica, 15:85 methanol/chloroform)
7. 7
   Sonstigeprovided a clear solid
8. 8
   FiltrationThe resulting precipitate was collected by filtration

Vorschrift

To an ice-cold, stirred solution of triphosgene (108 mg, 0.36 mmol) and diisopropylethylamine (0.6 mL, 3.3 mmol) in methylene chloride (2.0 mL) was added amino sulfone from step 4 (210 mg, 0.98 mmol) in methylene chloride (3.5 mL) dropwise. After 5 min a solution of dihydrochloride of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (401 mg, 0.98 mmol) was added and the reaction mixture was warmed until the solution became homogeneous. The reaction mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and saturated sodium chloride, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 15:85 methanol/chloroform) provided a clear solid. The solid was dissolved in methanol (1 mL), and treated with hydrochloric acid (0.3 mL of a 1.0 M solution in diethyl ether, 0.3 mmol). The resulting precipitate was collected by filtration to provide the title compound (38 mg): mp 130-134° C.; APCI MS m/z 538 [M+H]+.

Quelle