반응 #57457

반응 방정식

diisopropylethylamine

acetonitrile

1,3-dioxan-5-yl 4-nitrophenyl carbonate

tert-butyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate

→

white solid

수율 19.2%

1,3-dioxan-5-yl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate

수율 19.2%

용매

trifluoroacetic acid

반응 조건

후처리

1. 1
   기타The TFA was removed under vacuum
2. 2
   workup.DISSOLUTIONthe resulting residue was dissolved in ethyl acetate
3. 3
   세척washed with 5% aq. potassium carbonate solution, brine
4. 4
   건조dried over magnesium sulfate
5. 5
   농축concentrated to a residue
6. 6
   농축The reaction solution was concentrated to a residue
7. 7
   workup.DISSOLUTIONdissolved in ethyl acetate
8. 8
   세척washed with 1N HCl, 5% aq. potassium carbonate solution, brine
9. 9
   건조dried over magnesium sulfate
10. 10
    농축concentrated under vacuum
11. 11
    기타The crude residue was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and crystallization from ether and hexanes

실험 절차

tert-butyl N-((1S,2R)-1-benzyl-3-(cyclohexyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate (0.09 mmol, 50 mg) was stirred in 1 mL trifluoroacetic acid (TFA) at room temperature for 5 hours. The TFA was removed under vacuum, and the resulting residue was dissolved in ethyl acetate, washed with 5% aq. potassium carbonate solution, brine, dried over magnesium sulfate, and concentrated to a residue. The resulting free amine, 1,3-dioxan-5-yl 4-nitrophenyl carbonate (0.09 mmol, 25 mg), diisopropylethylamine (0.14 mmol, 0.024 mL), a crystal of N,N-dimethylaminopyridine, 4 Å molecular sieves and acetonitrile (0.5 mL) were combined and stirred at room temperature for 20 hours. The reaction solution was concentrated to a residue, dissolved in ethyl acetate, washed with 1N HCl, 5% aq. potassium carbonate solution, brine, dried over magnesium sulfate, and concentrated under vacuum. The crude residue was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and crystallization from ether and hexanes to yield 10 mg (19%) of white solid. Rf=0.2 (2:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.69 (2H,d), 7.29-7.18 (6H,m), 6.96 (2H,d), 5.01-4.93 (1H, m), 4.93-4.85 (1H,m), 4.74-4.70 (1H,m), 4.51-4.45 (1H,m), 4.22-4.11 (1H,m), 3.95-3.72 (7H,m), 3.86 (3H,s), 3.00-2.80 (3H,m), 2.10-1.97 (2H,m), 1.79-1.67 (2H,m), 1.61-1.53(2H,m), 1.38-1.02 (6H,m); MS (ESI): M+H=580.

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