Iodine → 1H-Pyrazole-4-carboxylic acid, 5-iodo-1,3-dimethyl-, methyl ester

Temperature

-45 °C

To a solution of methyl 1,3-dimethyl-1H-pyrazole-4-carboxylate (154 mg, 1 mmol) in dry tetrahydrofuran (10 mL) at −78° C., 2 M solution of BuLi (0.550 mL, 1.100 mmol) in pentane was added dropwise. The reaction mixture was then warmed to −45° C. and stirred for 1 h. It was then cooled to −78° C. and a solution of IODINE (279 mg, 1.100 mmol) in THF (2 mL) was added. The reaction mixture was warmed to RT and stirred for 1 h. It was then quenched with saturated NH4Cl solution and extracted with ethyl acetate (2×25 mL). The organic layers were combined, washed with brine, dried over MgSO4, and then concentrated in vacuo. The crude product was obtained as a brown thick oil. This material was then purified by preparative HPLC using CH3CN/H2O/TFA as solvent system. Homogeneous fractions were combined and concentrated in vacuo. The concentrate was then extracted with ethyl acetate and the extracts combined and dried over MgSO4. The suspension was then filtered and the filtrand evaporated under reduced pressure to give the title compound as a white solid, (137 mg, 0.460 mmol, 46.0% yield). MS m/z 281 (MH+), Retention time: 1.107 min. (basic). 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 2.45 (s, 3 H) 3.84 (s, 3H) 3.91 (s, 3H).

1. temperatureIt was then cooled to −78° C.
2. temperatureThe reaction mixture was warmed to RT
3. stirringstirred for 1 h
4. customIt was then quenched with saturated NH4Cl solution
5. extractionextracted with ethyl acetate (2×25 mL)
6. washwashed with brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe crude product was obtained as a brown thick oil
10. customThis material was then purified by preparative HPLC
11. concentrationconcentrated in vacuo
12. extractionThe concentrate was then extracted with ethyl acetate
13. dry with materialdried over MgSO4
14. filtrationThe suspension was then filtered
15. customthe filtrand evaporated under reduced pressure

ORD record

ord-8d0cfe0e04aa47e9a3fb39913b7e0619

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07652004B2