1-Tert-butyl 2-methyl pyrrolidine-1,2-dicarboxylate → 1-Boc-2-Formylpyrrolidine

Temperature

-78 °C

To a solution of pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.5 g) in toluene (40 mL) at −78° C. was added dropwise diisobutylaluminium hydride (20 mL of a 1.5 M solution in toluene) maintaining the temperature below −65° C. The reaction mixture was stirred at −78° C. for 2 h and then quenched with methanol (10 mL). The mixture was then diluted with diethyl ether (50 mL), potassium sodium tartrate tetrahydrate was added and the mixture stirred vigorously for 20 min at room temperature. The two phases were then separated and the aqueous layer extracted with dichloromethane (2×50 mL). The combined organics were then washed with brine (100 mL), dried (MgSO4), reduced in vacuo and purified by column chromatography to give 2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester as a pale yellow oil (2.687 g).

1. temperaturemaintaining the temperature below −65° C
2. customquenched with methanol (10 mL)
3. additionThe mixture was then diluted with diethyl ether (50 mL), potassium sodium tartrate tetrahydrate
4. additionwas added
5. stirringthe mixture stirred vigorously for 20 min at room temperature
6. customThe two phases were then separated
7. extractionthe aqueous layer extracted with dichloromethane (2×50 mL)
8. washThe combined organics were then washed with brine (100 mL)
9. dry with materialdried (MgSO4)
10. custompurified by column chromatography

ORD record

ord-11963fdbc1af4c28be0159d9768902a5

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802670B2