60% |
|
BQ. i. Methyl 3-(2-( (di-tert-butoxyphosphoryl)oxy)phenyl)propanoate: To a solution of methyl 3-(2-hydroxyphenyl)propionate (5 g; 30 mmol) in THF (102 mL), cooled at 0C, was added tetrazole (0.45M in MeCN; 92 mL; 0.042 mol) and <strong>[137348-86-8]di-tert-butyl diisopropylphosphoramidite</strong> (12 mL; 36 mmol). The reaction mixture was heated at 40C for 24 h. After cooling to 0C, 30% aq. ( (22 mL) was added dropwise at 0C, keeping IT below 10C. The solution was stirred for 1.5 h at 0C. Water (200 mL) was added. The aq. layer was extracted with EA (3 x 100 mL) and the org. layers were washed with 10% aq. NaHSOs (100 mL). The evaporation residue was purified by CC (Hept-EA) to afford the title compound as a colourless oil (6.2 g; 60% yield). NMR (d6- DMSO) delta: 7.35-7.20 (m, 3H); 7.1 1 (m, 1H); 3.60 (s, 3H); 2.94-2.85 (m, 2H); 2.66-2.56 (m, 2H); 1.45 (s, 18H). MS (ESI, m/z): 373.0 [M+H+] for Ci8H2906P; tR = 0.91 min. |
60% |
With 1H-tetrazole; In tetrahydrofuran; acetonitrile; at 0 - 40℃; for 24h; |
To a solution of methyl 3-(2-hydroxyphenyl)propionate (5 g; 30 mmol) in THF (102 mL),cooled at 0C, was added tetrazole (0.45M in MeCN, 92 mL; 0.042 mol) and di-tert-butyl15 diisopropylphosphoramidite (12 mL; 36 mmol). The reaction mixture was heated at 40Cfor 24 h. After cooling to 0C, 30% aq. H20 2 (22 mL) was added dropwise at 0C, keepingIT below 10C. The solution was stirred for 1.5 hat 0C. Water (200 mL) was added. Theaq. layer was extracted with EA (3 x 100 mL) and the org. layers were washed with 10%aq. NaHS03 (100 mL). The evaporation residue was purified by CC (Hept-EA) to afford20 the title compound as a colourless oil (6.2 g; 60% yield).1H NMR (d6- DMSO) o: 7.35-7.20 (m, 3H); 7.11 (m, 1H); 3.60 (s, 3H); 2.94-2.85 (m, 2H);2.66-2.56 (m, 2H); 1.45 (s, 18H).MS (ESI, m/z): 373.0 [M+H+] for C1sHz906P; tR = 0.91 min |
58% |
|
To a solution of methyl 3-(2-hydroxyphenyl)propionate (7.5 g; commercial) in THF (250ml) at ooc were added tetrazole (0.45 M in MeCN, 138 ml; commercial) and di-tert-butylN,N-diisopropylphosphoramidite (17.3 ml, commercial) and the solution was stirred at rtfor 2 h. Additional di-tert-butyl N,N-diisopropylphosphoramidite (6.63 ml, commercial) andtetrazole (0.45 M in MeCN, 18.5 ml; commercial) were added and the resulting mixture was stirred at rt for 3.5 h. The mixture was cooled to ooc and 30% aq. H202 (41 ml) wasadded drop wise. The mixture was stirred at ooc for 0.75 h. Water was added to themixture and the aq. layer was extracted with EA. The combined org. layers were washedwith water and brine and dried over MgS04. The solvents were removed under reducedpressure and the residue was purified by CC (HepUEA 99:1 to 0:1) affording the title compound as a yellow liquid (9.05 g; 58% yield). MS1 (ESI, m/z): 372.96 [M+W];tR = 0.91 min. 1 H NMR (500 MHz, CDC b) o: 1.53 (s, 18H), 2.67 (m, 2H), 3.03 (m, 2H),3.69 (s, 3H), 7.08 (t, J = 7.5 Hz, 1 H), 7.20 (m, 2H), 7.42 (d, J = 8.2 Hz, 1 H). |