Hydrochloric Acid → (2S,4R)-4-(((benzyloxy)carbonyl)amino)-1-((tert-butoxy)carbonyl)pyrrolidine-2-carboxylic acid

Step (a) Benzyl chloroformate (1.40 mL, 9.79 mmol) was added to a flask charged with (2S,4R)-1-tert-butyl 2-methyl 4-aminopyrrolidine-1,2-dicarboxylate hydrochloride salt (2.5 g, 8.9 mmol), DIEA (5.0 mL, 29 mmol), and THF (20 mL). The mixture was stirred for 5 minutes at ambient temperature and then quenched with saturated sodium bicarbonate (aq., 20 mL). The mixture was extracted with methylene chloride (40 mL) and the extract was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was diluted with methanol (30 mL) and 2N potassium hydroxide (10 mL, 20 mmol) and the mixture was stirred at ambient temperature for 3 hours. The reaction mixture then was concentrated to approximately one-half the volume and quenched with cold 1N hydrochloric acid (30 mL, 30 mmol). The mixture was extracted with methylene chloride (30 mL) and the extract dried over anhydrous sodium sulfate, filtered and concentrated to give (2S,4R)-4-(benzyloxycarbonylamino)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (2.51 g, 6.86 mmol) as a white solid.

1. customquenched with saturated sodium bicarbonate (aq., 20 mL)
2. extractionThe mixture was extracted with methylene chloride (40 mL)
3. dry with materialthe extract was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. stirringthe mixture was stirred at ambient temperature for 3 hours
7. concentrationThe reaction mixture then was concentrated to approximately one-half the volume
8. extractionThe mixture was extracted with methylene chloride (30 mL)
9. dry with materialthe extract dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-85a638b2336343d199eb00be349f0985

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791102B2