N-methyl-2-pyrrolidone → Methyl 3-cyano-4-hydroxybenzoate

HRID 2274056Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6].[Cu][C:14]#[N:15].CN1C(=O)CCC1>C(OCC)(=O)C>[C:14]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([O:7][CH3:8])=[O:6])#[N:15]

Participants

Conditions

Temperature: 200 °C

Procedure

To a mixture of methyl 3-bromo-4-hydroxybenzoate (1.78 g, 7.70 mmol) and copper(I) cyanide (0.897 g, 10.02 mmol) was added NMP (10 mL). The mixture was heated to 200° C. for 2 h under microwave irradiation. The mixture was diluted with ethyl acetate and quenched with 1 N aqueous HCl solution. After the addition of brine, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography. The combined fractions were concentrated under reduced pressure and triturated with cold water to provide the title compound as an off-white solid (0.63 g). LCMS m/z=178.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 3.92 (s, 3H), 6.55 (bs, 1H), 7.04 (d, J=8.72 Hz, 1H), 8.15 (dd, J=8.72, 2.15 Hz, 1H), 8.23 (d, J=1.89 Hz, 1H).

Workup

customquenched with 1 N aqueous HCl solution
additionAfter the addition of brine
customthe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate
dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
custompurified by silica gel column chromatography
concentrationThe combined fractions were concentrated under reduced pressure
customtriturated with cold water

Sources & evidence

ORD record: ord-b74788c68f3d4ab6bab2451453192d53
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126932B2

Reaction notes

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