Tetrahydrofuran → N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide

HRID 468713Notes

Reaction equation

[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH2:8])[CH:5]=[N:6][CH:7]=1.O1CCCC1.C[Mg]Br.[O:18]1[CH2:23][CH2:22][CH:21]([C:24](OC)=[O:25])[CH2:20][CH2:19]1>C1(C)C=CC=CC=1.ClCCl>[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH:8][C:24]([CH:21]2[CH2:22][CH2:23][O:18][CH2:19][CH2:20]2)=[O:25])[CH:5]=[N:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 5-bromo-4-methylpyridin-3-amine (128.9 mg, 0.6892 mmol) in tetrahydrofuran (4.0 mL, 49 mmol) at 0° C. was added 1.4 M of methylmagnesium bromide in toluene (0.55 mL). After stirring at 0° C. for 10 minutes, methyl tetrahydro-2H-pyran-4-carboxylate (92.00 g, 638.1 mmol) was added. The reaction mixture was stirred overnight while warming to room temperature. The reaction mixture was poured into dichloromethane, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 53.5 mg (26%) of N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide. LCMS (ESI): M+H=299.2.

Workup

stirringThe reaction mixture was stirred overnight
temperaturewhile warming to room temperature
washwashed with saturated aqueous NaHCO3
dry with materialdried over MgSO4
customevaporated in vacuo
customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane)

Sources & evidence

ORD record: ord-0d18ffedee634b008e7068232643a32e
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623889B2

Reaction notes

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