Iodoethane → Pyridine, 4-chloro-3-ethyl-5-iodo-

HRID 1267868Notes

Reaction equation

[CH2:1]([Li:5])[CH2:2]CC.[CH:6]([NH:9][CH:10]([CH3:12])[CH3:11])([CH3:8])[CH3:7].[Cl:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1[I:20].ICC>C1COCC1>[Li+:5].[CH3:7][CH:6]([N-:9][CH:10]([CH3:12])[CH3:11])[CH3:8].[Cl:13][C:14]1[C:15]([I:20])=[CH:16][N:17]=[CH:18][C:19]=1[CH2:1][CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

LDA was prepared by the addition of n-butyllithium (2.5 M in hexanes, 0.95 mL, 2.38 mmol) to a solution of diisopropylamine (0.345 mL, 2.42 mmol) in THF (5 mL) at −20° C. After 10 minutes, the solution was cooled to −78° C. 4-Chloro-3-iodo-pyridine (500 mg, 2.09 mmol) in THF (3 mL) was added dropwise, and the reaction stirred for 30 minutes Iodoethane (0.2 mL, 2.5 mmol) was added, and the reaction was stirred for 1 hour at −78° C., then 1 hour while warming to 0° C. The reaction was quenched with sat. NH4Cl, made basic with saturated NaHCO3, and extracted with ethyl acetate. Organics were washed with brine, dried over Na2SO4, and concentrated in vacuo. Purification by silica gel chromatography (20% ethyl acetate/hexanes) gave 429 mg (77%) of 4-chloro-3-ethyl-5-iodo-pyridine as a waxy white solid. 1H NMR (300 MHz, CDCl3) δ8.78 (s, 1H), 8.33 (s, 1H), 2.83 (q, 2H, J=7.5 Hz), 1.26 (t, 3H, J=7.5 Hz). Anal. (C7H7ClIN) C, H, N.

Workup

additionwas added
temperature1 hour while warming to 0° C
customThe reaction was quenched with sat. NH4Cl
extractionextracted with ethyl acetate
washOrganics were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customPurification by silica gel chromatography (20% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-dbc0f90b333c49baa120c94f7ade7d81
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06555539B2

Reaction notes

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