Potassium Hydroxide → 1,2-Pyrrolidinedicarboxylic acid, 3-hydroxy-, 1-(1,1-dimethylethyl) 2-methyl ester, (2R,3S)-rel-

Temperature

0 °C

To a solution of compound 1C (88.4 g, 0.253 mol) in anhydrous MeOH (700 mL) cooled to 0° C. was slowly added a freshly prepared 1N solution of KOH in anhydrous MeOH (367 mL, 0.367 mol) over 25 min through an addition funnel. After the addition, the light yellow solution was stirred at 0° C. for 2 h, and then the reaction was quenched by slow addition (over 25 min) of a solution of 1N HCl in dioxane/EtOAc (380 mL) through an addition funnel. The resulting white suspension was concentrated under reduced pressure to remove most of the solvent, and the remaining mixture was partitioned between water and EtOAc. The separated organic phase was washed with water (2×), saturated aqueous NaHCO3 (2×), water, brine, and then dried (Na2SO4). The filtrate was concentrated under reduced pressure to give a light yellow oily residue, which was chromatographed (silica gel) eluting first with 25-30% EtOAc/hexane, then 5% MeOH in 30% EtOAc/hexane to furnish compound 1D (44.6 g) as a pale yellow oil.

1. additionAfter the addition
2. customthe reaction was quenched by slow addition (over 25 min) of a solution of 1N HCl in dioxane/EtOAc (380 mL) through an addition funnel
3. concentrationThe resulting white suspension was concentrated under reduced pressure
4. customto remove most of the solvent
5. customthe remaining mixture was partitioned between water and EtOAc
6. washThe separated organic phase was washed with water (2×), saturated aqueous NaHCO3 (2×), water, brine
7. dry with materialdried (Na2SO4)
8. concentrationThe filtrate was concentrated under reduced pressure
9. customto give a light yellow oily residue, which
10. customwas chromatographed (silica gel)
11. washeluting first with 25-30% EtOAc/hexane

ORD record

ord-a86078a783c847ef911afbddd044b474

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07625923B2