Diisopropylethylamine → tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate

HRID 538733Notes

Reaction equation

[N:1]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3](O)=[O:4].C(N(C(C)C)CC)(C)C>C(#N)C>[CH:3]([C@@H:2]1[CH2:6][CH2:7][CH2:8][N:1]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:4]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 3 (11.80 g, 38.8 mmol), N-Boc-L-Pro-OH (10.02 g, 46.6 mmol), and diisopropylethylamine (7.02 g, 54.3 mmol) in acetonitrile (200 mL) was stirred at 50° C. for 10 h. The solvent was evaporated and the residue was partitioned between methylene chloride and H2O. The organic layer was separated and concentrated to dryness. The crude product was purified by silica gel column chromatography (hexanes/ethyl acetate=1/7 to 1/4 (v/v)) to provide 4 (11.53 g, 68% yield) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.84 (m, 1H), 7.48 (m, 2H), 5.58 (m, 1H), 4.40 (m, 1H), 3.60 (m, 1H), 3.40 (m, 1H), 3.18 (m, 1H), 3.04 (m, 1H), 2.37 (m, 2H), 2.04 (m, 1H), 1.96 (m, 1H), 1.46 (ds, 9H) ppm.

Workup

customThe solvent was evaporated
customthe residue was partitioned between methylene chloride and H2O
customThe organic layer was separated
concentrationconcentrated to dryness
customThe crude product was purified by silica gel column chromatography (hexanes/ethyl acetate=1/7 to 1/4 (v/v))

Sources & evidence

ORD record: ord-7ca54b1131504dfe8e9bdb4b13c4a981
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865756B2

Reaction notes

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