Hydrochloric Acid → HCID 50923086, compound

Temperature

0 °C

To a solution of ethyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate (500 mg, 2 mmol) in 5 mL DMF was added 60% NaH (400 mg, 10 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 1 h, followed by addition of 2-iodopropane (374 mg, 2.2 mmol). The reaction mixture was stirred at 0° C. for 7 h and quenched by ice water. The resulting mixture was extracted with EtOAc (2×15 mL) and the combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was dissolved in 2 mL MeCN and treated with lithium hydroxide (96 mg, 4 mmol) in 5 mL H2O for 30 min. The reaction mixture was acidified by 1N HCl to pH=5 and extracted with EtOAc (3×20 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to dryness. The residue was purified by prep HPLC to give the title compound as a white powder (170 mg, Yield 32.2%, two steps). 1H NMR (400 MHz, DMSO) δ 12.25 (s, 1H), 9.09 (d, J=2.8 Hz, 1H), 7.03 (s, 1H), 6.81 (s, 1H), 5.44 (d, J=9.2 Hz, 1H), 4.58-4.55 (m, 1H), 3.15-3.00 (m, 1H), 2.24 (s, 3H), 2.08-2.02 (m, 1H), 1.27 (d, J=5.6 Hz, 6H). MS (ESI) m/z=529 [2M+H]+.

1. stirringThe reaction mixture was stirred at 0° C. for 7 h
2. customquenched by ice water
3. extractionThe resulting mixture was extracted with EtOAc (2×15 mL)
4. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in 2 mL MeCN
7. extractionextracted with EtOAc (3×20 mL)
8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
9. concentrationconcentrated to dryness
10. customThe residue was purified by prep HPLC

ORD record

ord-4612e1ac77d74f6c96369e92cb27210e

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08343944B2