Potassium Carbonate → tert-butyl N-(4-cyano-2-vinylbenzyl)-N-methylglycinate

HRID 2410554Notes

Reaction equation

Br[C:2]1[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[CH:15][C:3]=1[CH2:4][N:5]([CH3:14])[CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].N[C:22](=NO)[C:23]1C=CC(CN(C)CC(OC(C)(C)C)=O)=C(Br)C=1.C(B1OC(C)(C)C(C)(C)O1)=C.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.O>[C:19]([C:17]1[CH:16]=[CH:15][C:3]([CH2:4][N:5]([CH3:14])[CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[C:2]([CH:22]=[CH2:23])[CH:18]=1)#[N:20]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of tert-butyl N-(2-bromo-4-cyanobenzyl)-N-methylglycinate (Intermediate 33 Step 1, 658 mg, 1.94 mmol), vinyl boronic acid pinacol ester (597 mg, 3.88 mmol), K2CO3 (536 mg, 3.88 mmol) and tetrakis-triphenylphosphine palladium(0) (224 mg, 0.19 mmol) was prepared in a mixture of dioxane/water (5:1; 6 mL) and heated at 100° C. for 18 hours. The reaction mixture was diluted with DCM/water and separated. The organic phase was passed through a hydrophobic frit and the solvents evaporated in vacuo. The residue was purified by flash chromatography (silica, iso-hexane/EtOAc) to afford the title compound (508 mg, 92%). 1H NMR (CDCl3, 400 MHz) δ 7.77 (1H, s), 7.58-7.43 (2H, m), 7.13 (1H, dd, J=17.4, 11.0 Hz), 5.69 (1H, d, J=17.4 Hz), 5.42 (1H, d, J=11.0 Hz), 3.80 (2H, s), 3.18 (2H, s), 2.36 (3H, s), 1.50 (9H, s).

Workup

customseparated
customthe solvents evaporated in vacuo
customThe residue was purified by flash chromatography (silica, iso-hexane/EtOAc)

Sources & evidence

ORD record: ord-92acb6e0f6014c22b095dd62e0277f83
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815919B2

Reaction notes

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