Carbon Dioxide → HCID 42127712, compound

A solution of 1-(2-chloro-7-fluoroquinolin-3-yl)ethanone (164 g, 733 mmol) in THF (1.34 L) was added to a solution of (+)-DIP-Cl (517.5 g, 2.2 eq) in THF (3.5 L) at −45° C. (dry ice and acetonitrile) dropwise. The reaction was slowly warmed up to rt overnight. The reaction was then quenched with acetone (750 mL) and 10% Na2CO3 (750 mL) at 0° C. and stirred at rt for 1 h before the addition of EtOAc (3.5 L). The mixture was warmed up to rt and washed with 10% Na2CO3 and water. The organic layer was dried with brine, concentrated and treated with hexane (1.0 L) and water (1.8 L). The mixture was stirred at rt for 40 min and filtered. The white solid was washed with water and hexane, dried in the air over night (143 g). This material was dried on the roto-evaporator at 60° C. for 4 h under high vacuum (2 mm Hg) to give a white powder of (R)-1-(2-chloro-7-fluoroquinolin-3-yl)ethanol (122 g, 73.7%). Chiral HPLC on AD column (isopropanol in hexane, 10%) showed ee>99%. Mass Spectrum (ESI) m/e=226 (M+1).

1. customThe reaction was then quenched with acetone (750 mL) and 10% Na2CO3 (750 mL) at 0° C.
2. temperatureThe mixture was warmed up to rt
3. washwashed with 10% Na2CO3 and water
4. dry with materialThe organic layer was dried with brine
5. concentrationconcentrated
6. additiontreated with hexane (1.0 L) and water (1.8 L)
7. stirringThe mixture was stirred at rt for 40 min
8. filtrationfiltered
9. washThe white solid was washed with water and hexane
10. customdried in the air over night (143 g)
11. customThis material was dried on the roto-evaporator at 60° C. for 4 h under high vacuum (2 mm Hg)

ORD record

ord-9f32a10443dc4587ad638b7397a086e5

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835432B2