Acetone → (alphaS,2R)-alpha-(Chloromethyl)-6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol

Temperature

0 °C

A solution of (−)-B-chlorodiisopinocampheylborane [(−)-DIP-Chloride™] (2.10 g, 6.55 mmoles) in toluene (7 ml) is cooled to 0° C. under nitrogen atmosphere. On the magnetically stirred solution is added in 3 hours a solution of 2-chloro-1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanone (1.0 g, 4.373 mmoles) in toluene (3 ml). At the end of the addition, the mixture is stirred at 0° C. for further 20 hours. On the reaction mixture is added acetone (0.5 g), followed by a 10% w/w (5 ml) aqueous solution of sodium carbonate, and then demi water (5 ml). The reactive mixture is heated to 20° C. at the end of the additions and transferred in a separator funnel. The mixture is diluted with demi water (5 ml) and toluene (5 ml) and phases are separated. The organic layer is then washed with additional demi water (15 ml) and concentrated and anhydrified under vacuum to obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (98% de via GC). The product is purified by chromatography on silica using a toluene:ethyl acetate 9.5:0.5 eluting mixture. After separation, the product (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol is isolated as a colorless oil (0.31 g, 31%).

1. additionAt the end of the addition
2. temperatureThe reactive mixture is heated to 20° C. at the end of the additions
3. customtransferred in a separator funnel
4. customare separated
5. washThe organic layer is then washed with additional demi water (15 ml)
6. concentrationconcentrated
7. customto obtain crude (S*)-2-chloro-1-((R*)-6-fluoro-3,4-dihydro-2H-chromen-2-yl)-ethanol (98% de via GC)
8. customThe product is purified by chromatography on silica using a toluene:ethyl acetate 9.5:0.5 eluting mixture
9. customAfter separation

ORD record

ord-b07a81cd900846d8b2dc1730b564f24f

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08084629B2