Sodium hydride → 3-Bromo-2-(cyclopropylmethoxy)-5-methylsulfonylpyridine

HRID 575785Notes

Reaction equation

[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Br:8][C:9]1[C:10](Cl)=[N:11][CH:12]=[C:13]([S:15]([CH3:18])(=[O:17])=[O:16])[CH:14]=1>CN(C=O)C>[Br:8][C:9]1[C:10]([O:5][CH2:4][CH:1]2[CH2:3][CH2:2]2)=[N:11][CH:12]=[C:13]([S:15]([CH3:18])(=[O:16])=[O:17])[CH:14]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of cyclopropylmethanol (146 uL, 1.8 mmol) stirred in DMF (3 mL) at 0° C. was treated with NaH (75 mg, 1.9 mmol, 60% in mineral oil). After stirring at 0° C. for 30 min, the reaction mixture was treated with a solution of 3-bromo-2-chloro-5-methylsulfonylpyridine (400 mg, 1.5 mmol) in DMF (3 mL) by dropwise addition. After the ice bath was removed, the mixture was stirred at rt for 14 h. The reaction mixture was treated with water and extracted with EtOAc (30 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography using a gradient of EtOAc (5 to 85%) in hexanes to give the title compound (298 mg, 65%). LCMS (M+H)+=307.

Workup

customAfter the ice bath was removed
stirringthe mixture was stirred at rt for 14 h
additionThe reaction mixture was treated with water
extractionextracted with EtOAc (30 mL×2)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-cc9d759e6c7f466dbfdc87b1c18f22a7
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09034900B2

Reaction notes

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