HCID 81430592, compound → Methyl 3-bromo-5-cyanobenzoate

HRID 1771713Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12](=O)[NH2:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]>O=P(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]#[N:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

Conditions

Temperature: 100 °C

Procedure

To methyl 3-bromo-5-carbamoyl-benzoate (2.8 g, 10.8 mmol, 1.0 eq) was added POCl3 (30 mL) and the reaction heated at 100° C. overnight. The POCl3 was removed under reduced pressure, water was added and the aqueous layer extracted with EtOAc. The combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo to afford a crude residue which was purified by column chromatography (petroleum ether:EtOAc, 20:1) to give methyl 3-bromo-5-cyano-benzoate (2.5 g, 96%). This material was dissolved in THF (30 mL) and LiOH.H2O (1.7 g, 41.6 mmol, 1.54 eq) and H2O (10 mL) were added. The mixture was stirred at room temperature overnight. The THF was removed under reduced pressure and the aqueous phase acidified with diluted HCl and extracted with EtOAc. The combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (CH2Cl2: MeOH, 50:1) to give the title compound as a white solid (2 g, 85%).

Workup

customThe POCl3 was removed under reduced pressure, water
additionwas added
extractionthe aqueous layer extracted with EtOAc
dry with materialThe combined organic extracts were dried (Na2SO4)
filtrationfiltered
customevaporated in vacuo
customto afford a crude residue which
customwas purified by column chromatography (petroleum ether:EtOAc, 20:1)

Sources & evidence

ORD record: ord-3546e09a696f409ba2535a6c729bdbe7
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249085B2

Reaction notes

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