Allyl bromide → 1-tert-Butyl 2-methyl (2S,4R)-4-{[6-(allyloxy)pyridin-2-yl]oxy}pyrrolidine-1,2-dicarboxylate

HRID 1255524Notes

Reaction equation

[OH:1][C:2]1[N:7]=[C:6]([O:8][C@H:9]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C:21]([O:23][CH3:24])=[O:22])[CH2:10]2)[CH:5]=[CH:4][CH:3]=1.[CH2:25](Br)[CH:26]=[CH2:27].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1>[CH2:27]([O:1][C:2]1[N:7]=[C:6]([O:8][C@H:9]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[C@H:11]([C:21]([O:23][CH3:24])=[O:22])[CH2:10]2)[CH:5]=[CH:4][CH:3]=1)[CH:26]=[CH2:25]

Participants

Conditions

Temperature: 60 °C

Procedure

A 500 mL round bottom flask under nitrogen was charged with the product of Step 4 (4.95 g, 14.63 mmol), tetrahydrofuran (200 ml), allyl bromide (2.53 ml, 29.3 mmol), and cesium carbonate (4.77 g, 14.63 mmol). Heated in a 60° C. oil bath for 18 hours. HPLC/MS o.k. Cooled. Evaporated. Added 2.5% potassium bisulfate. Extracted three times with ethyl acetate, washed combined organic portions with brine, dried with anhydrous magnesium sulfate, filtered and rotary evaporated filtrate. Subjected to flash column chromatography eluting with 70 hexane/30 ethyl acetate. Evaporation of fractions containing product gave the title compound as a pale oil. (4.56 g, 12.05 mmol, 82% yield). LCMS (ES+) m/z 379.3 (M+H)+.

Workup

temperatureCooled
customEvaporated
additionAdded 2.5% potassium bisulfate
extractionExtracted three times with ethyl acetate
washwashed
dry with materialdried with anhydrous magnesium sulfate
filtrationfiltered
washeluting with 70 hexane/30 ethyl acetate
customEvaporation of fractions
additioncontaining product

Sources & evidence

ORD record: ord-70115e8e75d14c688c0b19ad74d2b116
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461107B2

Reaction notes

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