반응 #54010

반응 방정식

[2-hydroxy-3-methyl-1-(3-oxo-propylcarbamoyl)-butyl]-carbamic acid benzyl ester

ethyl (2R,3R)-2-amino-3-hydroxy-3-[(2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate

Acetic acid

sodium triacetoxyborohydride

→

ethyl (5S)-12-[(R)-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxy-2-methylpropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   기타The reaction mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate solution
2. 2
   기타the aqueous layer was separated
3. 3
   추출extracted with ethyl acetate (2×75 ml)
4. 4
   세척The combined extracts were washed with saturated sodium chloride solution
5. 5
   건조dried over sodium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated in vacuo
8. 8
   기타The residue was purified by preparative HPLC (250×21 mm Phenomenex Prodigy ODS3 column eluted with 10-90% acetonitrile in water containing 0.02% trifluoroacetic acid over 72 minutes)

실험 절차

A solution of [2-hydroxy-3-methyl-1-(3-oxo-propylcarbamoyl)-butyl]-carbamic acid benzyl ester (313 mg, 0.93 mmol, obtained from Reference Example 14) and ethyl (2R,3R)-2-amino-3-hydroxy-3-[(2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate [400 mg, 0.93 mmol, obtained by hydrogenation of ethyl (2R,3R)-2-{[(benzyloxy)carbonyl]amino}-3-{[(benzyloxy)carbonyl]oxy}-3-[(2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate (from Reference Example 41)] in anhydrous tetrahydrofuran (7 ml) was stirred at room temperature under a nitrogen atmosphere for 15 minutes. Acetic acid (53 μl) and sodium triacetoxyborohydride (395 mg, 1.86 mmol) were added, and the resulting solution was stirred for 3 hours. The reaction mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate solution and the aqueous layer was separated and extracted with ethyl acetate (2×75 ml). The combined extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative HPLC (250×21 mm Phenomenex Prodigy ODS3 column eluted with 10-90% acetonitrile in water containing 0.02% trifluoroacetic acid over 72 minutes) to provide ethyl (5S)-12-[(R)-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxy-2-methylpropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate as white amorphous solid.

출처