Boron trifluoride etherate → HCID 69419011, compound

Temperature

-40 °C

To a stirred suspension of copper bromide-dimethylsulfide complex (2.15 g, 10.4 mmol) in dry Et2O (40 mL), cooled to −40° C., was added dropwise ethyl magnesium chloride (2M in Et2O; 5.22 mL, 10.4 mmol; Aldrich 300330) under an argon atmosphere. After stirring for 45 min, the mixture was cooled to −78° C., followed by dropwise addition of boron trifluoride etherate (1.32 mL, 10.4 mmol) and stirring for 15 min. Then, a solution of (S)-5-acetoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.00 g, 3.48 mmol, prepared as described in Scheme B1) in dry Et2O (10 mL) was added dropwise to result in a black suspension. The reaction mixture was stirred for 15 min and subsequently was allowed to warm up to RT over a period of 1 h. The reaction was quenched by addition of a (1:1)-mixture of a saturated aqueous NH4Cl solution and a concentrated aqueous NH3 solution (10 mL), followed by stirring for 30 min. The organic layer was separated, and the aqueous phase was extracted with Et2O (2×50 mL). The combined organics were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 2:8) to afford the title compound (contained less than 10% of the minor (2S,5S)-diastereoisomer according to 1H-NMR). TLC Rf (EtOAc/c-hexane 1:3)=0.48.

1. temperaturethe mixture was cooled to −78° C.
2. stirringstirring for 15 min
3. customto result in a black suspension
4. stirringThe reaction mixture was stirred for 15 min
5. temperatureto warm up to RT over a period of 1 h
6. customThe reaction was quenched by addition of a (1
7. stirringby stirring for 30 min
8. customThe organic layer was separated
9. extractionthe aqueous phase was extracted with Et2O (2×50 mL)
10. dry with materialThe combined organics were dried (Na2SO4)
11. customevaporated under reduced pressure
12. customThe residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane 2:8)

ORD record

ord-7217c7c0559d4d3c8fd6d2899bf38eb4

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085555B2