Imidazole → tert-Butyl 3-iodopyrrolidine-1-carboxylate

A round bottom flask was charged with 3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (5.0 g, 0.027 mol), triphenylphosphine (10.5 g, 0.0401 mol), iodine (10.16 g, 0.0401 mol), imidazole (2.72 g, 0.0401 mol), and methylene chloride (90 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered, and the collected solids were washed with methylene chloride. The combined organic layers were concentrated. The resulting crude product was dissolved in ethyl acetate, and the organic phase was washed with water. The ethyl acetate layer was washed with a 3:1 mixture of water and methanol to remove triphenylphosphine oxide. The ethyl acetate layer was then washed with brine, dried over anhydrous MgSO4, filtered, and concentrated. The crude product was loaded onto a 330 gram silica gel column. Flash chromatography afforded 3-iodo-pyrrolidine-1-carboxylic acid tert-butyl ester (6.9 g, 87%). 1H NMR (400 MHz, CDCl3) δ ppm 4.31-4.42 (m, 1H), 3.84 (dd, J=12.60, 6.30 Hz, 1H), 3.67-3.79 (m, 1H), 3.54-3.64 (m, 1H), 3.40-3.49 (m, 1H), 2.20-2.32 (m, 2H), 1.48 (s, 8H). MS cald. for C5H71NO2 [(M-C4H9)+] 241, obsd. 241.7, 282.7 [(M-C4H9+41)+].

1. filtrationThe reaction mixture was filtered
2. washthe collected solids were washed with methylene chloride
3. concentrationThe combined organic layers were concentrated
4. dissolutionThe resulting crude product was dissolved in ethyl acetate
5. washthe organic phase was washed with water
6. washThe ethyl acetate layer was washed with a 3:1 mixture of water and methanol
7. customto remove triphenylphosphine oxide
8. washThe ethyl acetate layer was then washed with brine
9. dry with materialdried over anhydrous MgSO4
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-d4d2f7db057b492dbc63c56ce698606d

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08470884B2