Iodine → Ethyl 5-(hydroxy(pyridin-2-yl)methyl)-4'-methylbiphenyl-3-carboxylate

HRID 1845270Notes

Reaction equation

[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.II.[CH:11]([C:13]1[CH:14]=[C:15]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:16]=[C:17]([C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)[CH:18]=1)=[O:12]>O1CCCC1>[OH:12][CH:11]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1)[C:13]1[CH:14]=[C:15]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:16]=[C:17]([C:19]2[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=2)[CH:18]=1

Participants

Conditions

Temperature: 0 °C

Procedure

The Grignard reagent was generated by treatment of magnesium (100 mg, 4.3 mmol) with a solution of 2-bromopyridine (600 mg, 3.8 mmol) and iodine (30 mg) in tetrahydrofuran (5 mL) under nitrogen at 60° C. for 1 hour. The mixture was cooled at 0° C. and ethyl 5-formyl-4′-methylbiphenyl-3-carboxylate (332 mg, 1.24 mmol) was added. The reaction mixture was stirred at 0° C. for 2 h and then quenched by addition of 3 mL of 2 N aq. H2SO4. The mixture was extracted with EtOAc (20 mL×2). The combined organic layers were washed with 1 N aq. NaOH, brine, dried over anhydrous MgSO4, filtered, and concentrated. The residue was chromatographed to yield a yellow oil.

Workup

customquenched by addition of 3 mL of 2 N aq. H2SO4
extractionThe mixture was extracted with EtOAc (20 mL×2)
washThe combined organic layers were washed with 1 N aq. NaOH, brine
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was chromatographed
customto yield a yellow oil

Sources & evidence

ORD record: ord-28891a6ad6534c45b9ccb2fd558cab2a
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946439B2

Reaction notes

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