Dimethylformamide → {2-[3-Cyano-4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 474734Notes

Reaction equation

[C:1]([O:5][C:6](=[O:28])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=2)=[C:12](Br)[CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:29][N:30](C)C=O>O.[C-]#N.[Zn+2].[C-]#N.[Zn]>[C:1]([O:5][C:6](=[O:28])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][N:18]=2)=[C:12]([C:29]#[N:30])[CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

{2-[3-bromo-4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (1.734 mmol, 1 eq), zinc cyanide (1.734 mmol, 1 eq), bis(tri-tbutylphosphine)palladium(0) (1.561 mmol, 0.9 eq) and zinc (0.173 mmol, 0.1 eq) were dissolved in N,N-dimethylformamide (48 ml) and heated in microwave Biotage Initiator at 120° C. for 3 min. Reaction mixture was diluted with water (200 ml) and extracted with EtOAc (7×15 ml). Crude product was purified on Biotage SP1 Snap Si 25; 25 ml/min in the gradient of MeOH in DCM: 0-30% for 30 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product {2-[3-cyano-4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (0.442 mmol, yield=25%, purity=91%). [M+H]+=408.35 1H NMR (300 MHz, CDCl3) δ/ppm 1.38 (s, 9H), 2.84 (s, 2H), 3.31-3.46 (m, 2H), 4.53-4.70 (m, 1H), 7.22 (s, 2H), 7.43-7.54 (m, 2H), 7.91-8.00 (m, 1H), 8.34-8.41 (m, 1H)

Workup

customReaction mixture
extractionextracted with EtOAc (7×15 ml)
customCrude product was purified on Biotage SP1 Snap Si 25
customevaporated in vacuo

Sources & evidence

ORD record: ord-793ef78417a44676a30404207c473be4
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637536B2

Reaction notes

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