Methyl iodide → (2S,3R)-3-Hydroxy-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Temperature

-20 °C

To a solution of (2S,3R)—N-tert-butyloxycarbonyl-3-hydroxy-2 pyrrolidinecarboxylic acid methyl ester (1D) (1.13 g, 4.61 mmol) in THF (73 mL) at −78° C. was slowly added a 1.8 M solution of LDA (7.70 mL, 13.86 mmol). After stirring for 1 h, iodomethane (2.87 mL, 46.10 mmol) was added, and the reaction was stirred for 1 h at −78° C., before warming gradually to −20° C. for 3 h, and then was stored at −40° C. overnight. After quenching with saturated aqueous NH4Cl, water and EtOAc were added and the layers were separated. The organic layer was washed with brine, and the aqueous layer was extracted with EtOAc. The combined organics were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified using preparative HPLC (Luna C-18, 21.2×250 mm, eluting with 50-90% solvent B (A=90% H2O—10% MeOH and B=10% H2O—90% MeOH) over 30 min; Flow rate at 10 mL/min. UV detection at 220 nm) to provide a mixture of the starting material and its epimer as a yellow oil (490 mg) and the title compound as a yellow oil (362 mg); LC/MS m/z 260 [M+H]+.

1. stirringthe reaction was stirred for 1 h at −78° C.
2. waitwas stored at −40° C. overnight
3. customAfter quenching with saturated aqueous NH4Cl, water and EtOAc
4. additionwere added
5. customthe layers were separated
6. washThe organic layer was washed with brine
7. extractionthe aqueous layer was extracted with EtOAc
8. dry with materialThe combined organics were dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified
12. washeluting with 50-90% solvent B (A=90% H2O—10% MeOH and B=10% H2O—90% MeOH) over 30 min
13. customUV detection at 220 nm) to provide

ORD record

ord-c5dbccf2e550441dac52331759bf20c5

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07405234B2