반응 #54008

반응 방정식

[(1S,2S)-2-hydroxy-1-(3-oxo-propylcarbamoyl)-propyl]-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

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

sodium triacetoxyborohydride

→

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

수율 46.0%

용매

tetrahydrofuran

Acetic acid

반응 조건

후처리

1. 1
   workup.STIRRINGthe resulting solution was stirred under nitrogen for an additional 2.5 hours
2. 2
   기타The reaction mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate solution
3. 3
   기타the aqueous layer was separated
4. 4
   추출extracted with ethyl acetate (2×75 ml)
5. 5
   세척The combined extracts were washed with saturated sodium chloride solution
6. 6
   건조dried over sodium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated in vacuo
9. 9
   기타The residue was chromatographed (flash column, silica gel, 5% methanol in methylene chloride)

실험 절차

A solution of [(1S,2S)-2-hydroxy-1-(3-oxo-propylcarbamoyl)-propyl]-carbamic acid benzyl ester (215 mg, 0.699 mmol, obtained from Reference Example 18) and a mixture of 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 and ethyl (2R,3R)-2-amino-3-hydroxy-3-[(2S,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate (300 mg, 0.699 mmol) in anhydrous tetrahydrofuran (3 ml) were stirred at room temperature under a nitrogen atmosphere for 15 minutes. Acetic acid (40 μl) and sodium triacetoxyborohydride (0.296 mg, 1.4 mmole) were added and the resulting solution was stirred under nitrogen for an additional 2.5 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 chromatographed (flash column, silica gel, 5% methanol in methylene chloride) to provide ethyl (5S)-12-[(R)-[(2R,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (230 mg, 46%) as a white solid.

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