Phosphate → Imidazo[1,2-a]quinoxaline-2-carboxaldehyde

Temperature

0 °C

(5R,6RS)-6-((RS)-Acetoxy imidazo[1,2-a]quinoxalin-2-ylmethyl)-6-bromo-7-oxo-4-thia-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (951 mg) and 10% Pd—C (50% wet, 477 mg) were added to a mixture of THF (48 mL) and 0.5 mol/L phosphate buffer (pH 6.5, 48 mL). The mixture was hydrogenated at 400 kPa at room temperature for 4 h. The reaction solution was filtered and Pd—C was washed with water and n-butanol. The reaction mixture was cooled to 0° C. and 1 N NaOH was added to adjust the ph to 8.5. The aqueous layer was separated and then the organic layer was extracted with water. The combined aqueous layer was concentrated to 57 g and applied to Diaion HP-21 resin (60 mL, Mitsubishi Kasei Co. Ltd.) column chromatography. After adsorbing, the column was eluted with water and then 5, 10, 15 and 20% acetonitrile:water solution (each 60 mL). The combined fractions were concentrated under high vacuum at 35° C. and lyophilized to give the title compound as a yellow amorphous solid, yield 148 mg (26.1%), mp 300° C. (dec). 1H NMR (D2O) δ 5.92 (s, 1H), 6.23 (s, 1H), 6.66 (s, 1H), 7.11-7.22 (m, 3H), 7.25 (d, 1H, J=7.9 Hz), 7.50 (s, 1H), 8.03 (s, 1H); IR (KBr) 3413, 1748, 1592, 1553 cm−1; Imax (H2O) 340, 293, 237, 218 nm.

1. filtrationThe reaction solution was filtered
2. washPd—C was washed with water and n-butanol
3. addition1 N NaOH was added
4. customThe aqueous layer was separated
5. extractionthe organic layer was extracted with water
6. concentrationThe combined aqueous layer was concentrated to 57 g
7. washthe column was eluted with water
8. concentrationThe combined fractions were concentrated under high vacuum at 35° C.

ORD record

ord-0237b6579cb14f00893c212010c9ef00

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07691842B2