Hydrogen Bromide → 2-Bromo-1-(6-methoxy-4-methyl-pyridin-3-yl)-propan-1-one

HRID 1671322Notes

Reaction equation

[BrH:1].[CH3:2][O:3][C:4]1[N:9]=[CH:8][C:7]([CH:10]([OH:13])[CH2:11][CH3:12])=[C:6]([CH3:14])[CH:5]=1.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O.[Cu](Br)Br>[Br:1][CH:11]([CH3:12])[C:10]([C:7]1[CH:8]=[N:9][C:4]([O:3][CH3:2])=[CH:5][C:6]=1[CH3:14])=[O:13]

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred suspension of copper (II) bromide (499 mg, 2.23 mmol, 2 eq.) in EtOAc is added HBr (33% in acetic acid, 0.368 ml, 2.25 mmol, 2 eq.) followed by 1-(6-methoxy-4-methyl-pyridin-3-yl)-propan-1-ol (200 mg, 1.12 mmol, 1 eq.). The mixture is heated at 70° C. for 12 hrs. After cooling to RT the mixture is poured into 2M Na2CO3 (50 ml) and extracted with EtOAc (2×50 ml). The combined extracts are washed successively with 2M Na2CO3, water and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting crude residue is purified by column chromatography on silica gel eluting with 10% EtOAc/iso-hexane to yield 2-bromo-1-(6-methoxy-4-methyl-pyridin-3-yl)-propan-1-one as a clear oil. MS: m/z 257.9 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 1.90 (d, 3H), 2.50 (s, 3H), 4.0 (s, 3H), 2.33 (s, 3H), 5.20 (q, 1H), 6.65 (s, 1H), 8.65 (s, 1H).

Workup

temperatureAfter cooling to RT the mixture
extractionextracted with EtOAc (2×50 ml)
washThe combined extracts are washed successively with 2M Na2CO3, water and brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe resulting crude residue is purified by column chromatography on silica gel eluting with 10% EtOAc/iso-hexane

Sources & evidence

ORD record: ord-14164ec9f0f1426c837b3fe72e17125b
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07994203B2

Reaction notes

Loading…