반응 #54021

반응 방정식

sodium triacetoxyborohydride

tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2,4-dioxo -3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

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

N-CBZ-D-leucine

sodium carbonate

→

tert-butyl (5R,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

수율 42.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.STIRRINGthe resulting solution was stirred under nitrogen for an additional 2.5 hours
2. 2
   추출the aqueous layer was extracted with ethyl acetate (3×50 ml)
3. 3
   세척The combined extracts were washed with saturated sodium chloride solution
4. 4
   건조dried over sodium sulfate
5. 5
   여과filtered
6. 6
   농축concentrated in vacuo
7. 7
   기타The residue was chromatographed (flash column, silica gel, 2.5% methanol in methylene chloride)

실험 절차

A solution of tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (62 mg, 0.086 mmol, obtained from Reference Example 6) and [(1R)-3-methyl-1-(3-oxo-propylcarbamoyl)butyl]-carbamic acid benzyl ester (33 mg, 0.103 mmol, obtained from N-CBZ-D-leucine in an similar manner described in Reference Example 15 and 16) in anhydrous tetrahydrofuran was stirred at room temperature under a nitrogen atmosphere for 15 minutes. Acetic acid (2 drops) and sodium triacetoxyborohydride (36 mg, 0.17 mmol) were added and the resulting solution was stirred under nitrogen for an additional 2.5 hours. The reaction mixture was basified to pH 9 with aqueous sodium carbonate solution and the aqueous layer was extracted with ethyl acetate (3×50 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, 2.5% methanol in methylene chloride) to provide tert-butyl (5R,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (37 mg, 42%) as a white amorphous solid.

출처