Sodium Azide → 1-tert-butyl 2-methyl (2R,4R)-4-azidopyrrolidine-1,2-dicarboxylate

HRID 244348Notes

Reaction equation

[N-:1]=[N+:2]=[N-:3].[Na+].[CH3:5][O:6][C:7]([C@H:9]1[CH2:13][C@H:12](Br)[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:8]>CN(C)C=O.O>[CH3:5][O:6][C:7]([C@H:9]1[CH2:13][C@@H:12]([N:1]=[N+:2]=[N-:3])[CH2:11][N:10]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:8]

Participants

Conditions

Temperature: 72.5 °C

Procedure

Add sodium azide (157 g, 2.39 mol) to (2R,4S)-4-bromo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (370 g, 1.20 mol) in N,N-dimethylformamide (2.5 L) and heat at 70-75° C. for 16 h under nitrogen. Cool to room temperature, dilute with water (5 L), and extract with ethyl acetate (3 L). Wash with brine (2 L). Extract the brine layer with ethyl acetate (3 L), combine the organic layers, dry over sodium sulfate, filter and concentrate to obtain an oil (324.5 g). Dissolve the material in ether (2 L), wash with water (2×2 L), dry over sodium sulfate, filter, and concentrate to obtain 261.2 g of a dark yellow oil. Back-extract the aqueous layer with ether (2×2 L), dry over sodium sulfate, filter, and concentrate to obtain an additional 7.3 g of product. Overall yield 268.5 g (83%). [α]D20+39.5 (c=1.0 in methanol). 1H NMR (400 MHz, CDCl3) δ 1.40-1.41 (s, 9H), 2.09-2.13 (m, 1H), 2.40-2.44 (m, 1H), 3.37-3.45 (m, 1H), 3.61-3.65 (m, 1H), 3.67-3.69 (s, 3H), 4.09-4.15 (m, 1H), 4.25-4.38 (m, 1H).

Workup

temperatureCool to room temperature
extractionextract with ethyl acetate (3 L)
washWash with brine (2 L)
extractionExtract the brine layer with ethyl acetate (3 L)
dry with materialdry over sodium sulfate
filtrationfilter
concentrationconcentrate

Sources & evidence

ORD record: ord-7c87413dd4ec47c980a29149fe7de81b
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658638B2

Reaction notes

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