Boron trifluoride → HCID 58689703, compound

Temperature

-70 °C

To a solution of 2-bromoanisole (11.21 g, 59.93 mmol) in dry tetrahydrofuran (Aldrich sure-seal, 160 mL) at −70° C. was added n-butyllithium (1.05 eq. of 2.5M in hexanes, freshly opened, 25.2 mL, 62.93 mmol). After 30 mins stirring at −70° C., BF3 etherate (9.36 g, 65.9 mmol) was added. After a further 30 mins at −70° C. (R)-epichlorohydrin (5.55 g, 59.93 mmol) in tetrahydrofuran (50 mL) was added. After 2 hrs the reaction mixture was quenched by the addition of 10% aqueous ammonium chloride (50 mL) followed by warming to ambient temperature. ethyl acetate was added and the organic phase washed with water and brine. Drying (Na2SO4) and concentration under reduced pressure afforded the crude product as a pale yellow semi-solid (9.88 g). Purification by silica gel chromatography (5% ethyl acetate/iso-hexane) afforded the intermediate (e), (R)-1-chloro-3-(2-methoxyphenyl)-2-propanol, as colorless oil (6.04 g, 50% yield).

1. customAfter 2 hrs the reaction mixture was quenched by the addition of 10% aqueous ammonium chloride (50 mL)
2. temperatureby warming to ambient temperature
3. additionethyl acetate was added
4. washthe organic phase washed with water and brine
5. customDrying
6. concentration(Na2SO4) and concentration under reduced pressure
7. customafforded the crude product as a pale yellow semi-solid (9.88 g)
8. customPurification by silica gel chromatography (5% ethyl acetate/iso-hexane)

ORD record

ord-89f8efb764dc4680be4d53c0b770ca14

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07323466B2