Boron Trichloride → HCID 71152127, compound

To a solution of tert-butyl ((3aR,5S,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-formyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.35 g, 0.83 mmol) in anhydrous THF (15 mL), at 0° C. and under N2, was added MeMgBr (1.4 M in THF/toluene, 3.0 mL, 4.2 mmol). After addition the mixture was stirred at room temperature for 2 h. The reaction was quenched with saturated NaHCO3 aqueous solution (30 mL), and then extracted with EtOAc (30 mL) and DCM (3×30 mL). The combined extract was dried over anhydrous Na2SO4. After filtration the solvent was evaporated under reduced pressure, and the residue was dried under high vacuum. To the residue and PMB (0.50 g, 3.4 mmol) in dry DCM (8 mL) at −78° C. under N2, was added BCl3 (1.0 M in DCM, 3.0 mL, 3.0 mmol). The mixture was stirred for ˜3 h while the temperature of the cooling bath slowly warmed to room temperature. The reaction mixture was cooled at −78° C., quenched with mixed MeOH/DCM, and then concentrated to dryness. The residue was purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH/DCM, 1:10), affording (3aR,5R,6R,7S,7aR)-7-fluoro-5-((R)-1-hydroxyethyl)-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-6-ol as a white solid (0.039 g, 19%). 1H NMR (400 MHz, CD3OD) δ 6.40 (d, J=6.7 Hz, 1H), 4.78 (td, J=3.6, 49.3 Hz, 1H), 4.40 (ddd, J=3.6, 6.6, 18.0 Hz, 1H), 4.00-3.89 (m, 2H), 3.79 (dd, J=3.2, 8.0 Hz, 1H), 2.86 (s, 3H), 1.19 (d, J=6.6 Hz, 1H); 13C NMR (100 MHz, CD3OD) δ 165.99, 91.11 (d, J=5.31 Hz), 90.74 (d, J=184.1 Hz), 76.85 (q, J=3.7 Hz), 71.64 (d, J=16.4 Hz), 68.64, 68.22 (d, J=16.9 Hz), 30.55, 17.74; MS, (ES, m/z) [M+H]+ 251.1.

1. additionAfter addition the mixture
2. customThe reaction was quenched with saturated NaHCO3 aqueous solution (30 mL)
3. extractionextracted with EtOAc (30 mL) and DCM (3×30 mL)
4. extractionThe combined extract
5. dry with materialwas dried over anhydrous Na2SO4
6. filtrationAfter filtration the solvent
7. customwas evaporated under reduced pressure
8. customthe residue was dried under high vacuum
9. stirringThe mixture was stirred for ˜3 h while the temperature of the cooling bath
10. temperatureslowly warmed to room temperature
11. temperatureThe reaction mixture was cooled at −78° C.
12. customquenched with mixed MeOH/DCM
13. concentrationconcentrated to dryness
14. customThe residue was purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH/DCM, 1:10)

ORD record

ord-93f4cd7e5e134cc987832ffe7d6dea08

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409924B2