Sodium Hydroxide → HCID 66653483, compound

Temperature

-15 °C

To a stifling solution of (R)-2-(3-methoxycarbonyl-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (98.6 g, 319.7 mmol) in MeOH (1000 mL) in a water bath at 15° C. add 10M NaOH aqueous solution (500 mL) portionwise over 5 min (exotherm to 37° C.) and stir the reaction at ambient temp for 20 h. Concentrate the reaction in vacuo at 35° C. to remove MeOH and give a suspension. Dilute the slurry with water (200 mL), cool to −15° C. in a dry ice/iPrOH bath and quench with addition of concentrated HCl (417 mL) over 1 h with vigorous mechanical stirring maintaining internal temp at −5° C., to a final pH of 1. Extract the cold suspension with EtOAc (2×1500 mL), and wash the organics with water (2×1000 mL) and brine (400 mL). Dry the organic layers (Na2SO4), and concentrate at 40° C. to a solid. Suspend this in hexane (750 mL) and filter to give 91.65 g of the product (R)-2-(3-Carboxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a solid.

1. customthe reaction at ambient temp for 20 h
2. concentrationConcentrate
3. customthe reaction in vacuo at 35° C.
4. customto remove MeOH
5. customgive a suspension
6. customquench with addition of concentrated HCl (417 mL) over 1 h with vigorous
7. stirringmechanical stirring
8. temperaturemaintaining internal temp at −5° C.
9. extractionExtract the cold suspension with EtOAc (2×1500 mL)
10. washwash the organics with water (2×1000 mL) and brine (400 mL)
11. dry with materialDry the organic layers (Na2SO4)
12. concentrationconcentrate at 40° C. to a solid
13. filtrationfilter

ORD record

ord-255a54e55fe44f22a7ee45db5250258e

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09079880B2