Methyl 3-bromo-4-(tert-butyl)benzoate → Methyl 4-tert-butyl-3-cyano-benzoate

HRID 1908086Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[C:12]([CH3:15])([CH3:14])[CH3:13])[C:5]([O:7][CH3:8])=[O:6].[C:16]([Cu])#[N:17]>CN(C=O)C.[C-]#N.[Na+]>[C:12]([C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[C:16]#[N:17])([CH3:15])([CH3:14])[CH3:13]

Participants

Conditions

Temperature: 110 °C

Procedure

Methyl 3-bromo-4-tert-butyl-benzoate (2.26 g, 4.17 mmol) was dissolved in dry DMF (2.1 mL) before CuCN (821 mg, 9.17 mmol) and NaCN (1.0 mg, 0.021 mmol) were added. The mixture was flushed with nitrogen and was stirred at 110° C. for 24 h. The reaction mixture was diluted with ethyl acetate (70 mL) and was washed with water. The organics were dried over sodium sulfate and were evaporated to dryness. The crude material was purified by column chromatography eluting with 0-10% ethyl acetate in hexanes to give methyl 4-tert-butyl-3-cyano-benzoate (390 mg, 43%). ESI-MS m/z calc. 217.1. found 218.5 (M+1)+; Retention time: 2.07 minutes (3 min run). NMR (400 MHz, CD3CN) δ 8.31 (d, J=1.8 Hz, 1H), 8.16 (dd, J=8.4, 2.0 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H), 3.92 (s, 3H), 1.55 (s, 9H).

Workup

additionwere added
customThe mixture was flushed with nitrogen
additionThe reaction mixture was diluted with ethyl acetate (70 mL)
washwas washed with water
dry with materialThe organics were dried over sodium sulfate
customwere evaporated to dryness
customThe crude material was purified by column chromatography
washeluting with 0-10% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-e4359dd7273842e49c1c4f3ffc1b42bb
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598164B2

Reaction notes

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