Dimethylformamide → (R)-3-(Methoxymethylcarbamoyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

Temperature

0 °C

(R)-1-N-Boc-β-Proline (700 mg, 3.3 mmol; (R)-pyrrolidine-1,3-dicarboxylic acid 1-t-butyl ester), HCTU (1.7 g, 4.1 mmol), HOBt (622 mg, 4.1 mmol), N,O-dimethyl-hydroxylamine HCl (1.6 g, 16.3 mmol) and DMF (10.0 mL, 129 mmol) were combined and cooled at 0° C. using an ice bath. DIPEA (5.7 mL, 32.5 mmol) was added slowly over 5 minutes. The mixture was allowed to warm to room temperature and stirred for 15 hours. The mixture was then diluted with sat. NaHCO3 (75 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with sat. NaCl (50 mL) and water (50 mL), dried over Na2SO4, filtered, and concentrated under high vacuum to yield 1.6 g of the crude product, which was purified by flash chromatography (12 g column, 10-100% EtOAc in hexanes over 16 minutes), and placed under high vacuum for 15 minutes to yield 723 mg of the title compound.

1. temperatureto warm to room temperature
2. extractionextracted with EtOAc (2×100 mL)
3. washThe combined organic layers were washed with sat. NaCl (50 mL) and water (50 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under high vacuum
7. customto yield 1.6 g of the crude product, which
8. customwas purified by flash chromatography (12 g column, 10-100% EtOAc in hexanes over 16 minutes)
9. waitplaced under high vacuum for 15 minutes

ORD record

ord-321eb0482a2b488e967abb3fb60897f8

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888386B2