Chloroacetic anhydride → HCID 42612215, compound

A solution of mannosamine hydrochloride (250 mg, 1.16 mmol) and sodium methoxide (1.16 ml of a 1 M methanolic solution) in dry MeOH (10 ml) was stirred for 1 h at room temperature, after which chloroacetic anhydride (991 mg, 5.80 mmol) was added. The resulting solution was stirred overnight at room temperature under an atmosphere of N2 and then quenched with H2O (5 ml) for 1 hour. The solution was neutralized with saturated NaHCO3 and concentrated, and the residue was filtered through a plug of silica gel eluting with 5:1 CHCl3/MeOH. The crude product obtained was dissolved in DMF (10 ml) and NaN3 (78 mg, 1.39 mmol) was added. After heating at reflux overnight, the solution was cooled and concentrated. Purification by silica gel chromatography eluting with a gradient of 50:1 to 6:1 CHCl3/MeOH afforded 179 mg of compound 20 (59% over two steps). The compound was peracetylated prior to incubation with cells as follows. A solution of 20 (25 mg, 0.095 mmol), acetic anhydride (1.0 ml, 11 mmol) and a catalytic amount of DMAP in pyridine (2 ml) was cooled to 0° C. The mixture was stirred overnight, warmed to rt, then diluted with CH2Cl2 (100 ml) and washed with 1 N HCl (3×50 ml), sat. NaHCO3 (1×50 ml), water (1×50 ml) and saturated NaCl (1×50 ml). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by silica gel chromatography eluting with a gradient of 1:10 to 1:2 EtOAc/hexanes to afford 39 mg (95%) of acetylated 20 (compound 36).

1. customquenched with H2O (5 ml) for 1 hour
2. concentrationconcentrated
3. filtrationthe residue was filtered through a plug of silica gel eluting with 5:1 CHCl3/MeOH
4. customThe crude product obtained
5. temperatureAfter heating
6. temperatureat reflux overnight
7. temperaturethe solution was cooled
8. concentrationconcentrated
9. customPurification by silica gel chromatography
10. washeluting with a gradient of 50:1 to 6:1 CHCl3/MeOH

ORD record

ord-4ecde3376b214090b3e0b2b718b5a348

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07667012B2