Electric Literature of 4934-99-0, These common heterocyclic compound, 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a solution of methyl 3- hydroxycyclobutanecarboxylate (2 g, 15.37 mmol), 5-methyl-4-nitro-lH-pyrazole (1 .95 g, 15.37 mmol) and PPh3 (6.05 g, 23.06 mmol) in THF (30 mL) was added dropwise DIAD (4.66 g, 23.06 mmol, 4.48 mL) at 0 C and degassed and purged with N2 for 3 times, and then the mixture was stirred at 25 C for 16 h under N2. The reaction mixture was concentrated under reduced pressure to remove THF. The residue was washed with PE:EtOAc (1 : 1, 30 mL), filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO?., PE:EtOAc =: 10: 1 to 5: 1) to give the mixture of trans-methyl 3-(5-methyi-4-nitro-pyrazol-l-yl)cyc3obutanecarboxylate and trans- methyl 3-(3-methy3-4~nitro-pyrazol~l -yl)cyclobutanecarboxylate as a white solid. LCMS: RT 0.729 min, m/z = 240,2 [M + H]+ To a solution of methyl 3-(5-methyi-4-nitro-py razol-l- yl)cyclobutanecarboxylate and methyl 3-(3-methyl-4-nitro-pyrazo3-l~yl)cyclobutanecarboxylate (1.7 g, 7.1 mmol, mixture) in MeOH (20 mL) was added NaBH4 (672 mg, 17.77 mmol) at 0 C. The mixture was stirred at 25 C for 2 h. The reaction mixture was quenched by addition of aq. NH4C1 (20 mL) at 0 C, and extracted with EtOAc (3 * 10 mL), washed with brine (5 mL), dried over Na SCX-i, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (SiO?., PE:EtOAc = 5: 1 to 1 : 1) to give the mixture of trans- [3~(5-methyl-4-nitro~pyrazol-l~yl)cyclobutyl]methanol and fr n.v-[3-(3-methyl-4-nitro-pyrazol-l -yl)cyclobutyl]methanol as a yellow solid. LCMS: RT 0.645 min, m/z == 212.2 [M + H]+.
The synthetic route of 4934-99-0 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; DENALI THERAPEUTICS INC.; ESTRADA, Anthony A.; FENG, Jianwen A.; LYSSIKATOS, Joseph P.; SWEENEY, Zachary K.; DE VICENTE FIDALGO, Javier; (271 pag.)WO2017/87905; (2017); A1;,
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