Methyl iodide → 3-Bromo-5-(2-methoxypropan-2-yl)pyridine

HRID 712687

Reaction equation

[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:10]([OH:13])([CH3:12])[CH3:11])[CH:7]=[N:8][CH:9]=1.I[CH3:15]>CN(C=O)C>[Br:3][C:4]1[CH:9]=[N:8][CH:7]=[C:6]([C:10]([O:13][CH3:15])([CH3:11])[CH3:12])[CH:5]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a mixture of NaH (240 mg, 6.02 mmol) in DMF (dry, 4 mL) at 0° C. is added the solution of 2-(5-bromo-pyridin-3-yl)-propan-2-ol (500 mg, 2.31 mmol) in DMF (dry, 4 mL). The mixture is stirred at 0° C. for 15 min then raised to room temperature and stirred for 1 h. The mixture is then cooled back to 0° C. and iodomethane (397 mg, 2.80 mmol) iss added. The reaction mixture is stirred at room temperature overnight and is quenched by adding water dropwise. The mixture is partitioned between DCM and water. The DCM phase is separated and then washed with water twice. The DCM phase is evaporated under high vacuum. The residue is separated by silica gel flash column (EtOAc/Hepane 0 to 40% gradient, then 40%) to obtain 371 mg 3-bromo-5-(1-methoxy-1-methyl-ethyl)pyridine.

Workup

temperaturethen raised to room temperature
stirringstirred for 1 h
temperatureThe mixture is then cooled back to 0° C.
stirringThe reaction mixture is stirred at room temperature overnight
customis quenched
additionby adding water dropwise
customThe mixture is partitioned between DCM and water
customThe DCM phase is separated
washwashed with water twice
customThe DCM phase is evaporated under high vacuum
customThe residue is separated by silica gel flash column (EtOAc/Hepane 0 to 40% gradient

Sources & evidence

ORD record: ord-3af60b42a4b848ca8fb5e516774f8b2f
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181272B2

Linked notes

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