Iodine → (3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl ester

HRID 1264229Notes

Reaction equation

[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].CN(C)CCN(C)C.C([Li])CCC.[I:28]I>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:14])[NH:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[I:28])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of pyridin-4-yl-carbamic acid tert-butyl ester (14.8 g, 76.3 mmol) (reference example 44b) in THF (300 mL) is added N,N,N′,N′-tetramethylethylene-diamine (34.5 mL, 230 mmol) and the solution cooled to −78° C. To this solution is added slowly (2.5M) n-butyllithium (91.5 mL, 230 mmol), the reaction temperature allowed to rise to −20° C. and the resulting mixture stirred for 1.5 hours. The mixture is cooled to −78° C. and a solution of iodine (29.04 g, 114 mmol) in THF (60 mL) is added then stirred for 10 min. The mixture is warmed to 20° C., stirred 30 min then diluted with ethyl acetate, washed with water, sat. sodium thiosulfate and brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluting with 20% ethyl acetate in hexanes) to give 17.7 g of title compound as a light yellow crystalline solid. 1H NMR (CDCl3) δ 1.54 (s, 9H), 7.03 (bs, 1H), 8.10 (d, J=6 Hz, 1H), 8.34 (d, J=6 Hz, 1H), 8.74 (s, 1H). MS (EI) m/z 320 (M+).

Workup

customto rise to −20° C.
temperatureThe mixture is cooled to −78° C.
stirringthen stirred for 10 min
temperatureThe mixture is warmed to 20° C.
stirringstirred 30 min
washwashed with water, sat. sodium thiosulfate and brine
dry with materialdried over MgSO4
concentrationconcentrated
customThe residue is purified by flash chromatography (eluting with 20% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-8452044c353842ad8e3a070cd851bd8b
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06541505B1

Reaction notes

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