Phosphate → HCID 21057706, compound

Freshly activated Zn dust (21.4 g) was added rapidly with 0.5 mol/L phosphate buffer (pH 6.5, 112 mL) to the THF (76 mL) and acetonitrile (36 mL) solution of crude (5R)-6-[acetoxy-(4,5-dihydro-6-thia-1,7a-diazainden-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester. The reaction vessel was covered with foil to exclude light. The reaction mixture was vigorously stirred for 1.5 h at room temperature. The reaction solution was cooled at 0° C., and then the pH was adjusted to 8.0. Ethyl acetate (56 mL) was added to the mixture and filtered through a pad of Celite. The pad was washed with water (150 mL). The aqueous layer was separated and then the organic layer was extracted with 0.5 mol/L phosphate buffer (pH 6.5, 2×30 mL). The combined aqueous layers were cooled at 0° C., and then the pH was adjusted to 8.0. The mixture was concentrated to 236 g, and then applied to Diaion HP-21 resin (480 mL, Mitsubishi Kasei Co. Ltd.) column chromatography. After adsorbing, the column was eluted with water (960 mL) and then acetonitrile aqueous solution (5%; 960 mL, 10%; 960 mL, 20%; 960 mL). The combined active fractions were concentrated under high vacuum at 35° C. and lyophilized to give the titled compound as a yellow amorphous solid (1.28 g, 40.5%, pH 7.45).

1. temperatureThe reaction solution was cooled at 0° C.
2. filtrationfiltered through a pad of Celite
3. washThe pad was washed with water (150 mL)
4. customThe aqueous layer was separated
5. extractionthe organic layer was extracted with 0.5 mol/L phosphate buffer (pH 6.5, 2×30 mL)
6. temperatureThe combined aqueous layers were cooled at 0° C.
7. concentrationThe mixture was concentrated to 236 g
8. washthe column was eluted with water (960 mL)
9. concentrationThe combined active fractions were concentrated under high vacuum at 35° C.

ORD record

ord-dffb8dd6b2c7466cba93562632d75279

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812014B2