Water → 5-(2-Amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)benzonitrile
Reaction equation
Br[C:2]1[C:3]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][N:13]=2)=[C:4]([CH2:8]CN)[CH:5]=[CH:6][CH:7]=1.[Cu]C#[N:24].O.C[N:27]1CC[CH2:29][C:28]1=O>>[NH2:27][CH2:28][CH2:29][C:6]1[CH:7]=[CH:2][C:3]([O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][N:13]=2)=[C:4]([CH:5]=1)[C:8]#[N:24]Participants
Procedure
A mixture of 2-[3-bromo-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl]-ethylamine (950 mg, 2.059 mmol) and copper(I)cyanide (239.78 mg, 2.677 mmol, 1.3 eq) were suspended in N-methylpyrrolidone (2.1 ml) was irradiated in microwave Biotage Initiator at 200° C. for 20 min. After cooling, water (20 ml) was added and extraction with EtOAc (3×15 ml) followed. Organic layers were combined, dried over Na2SO4/MgSO4, filtered off and evaporated in vacuo to give crude 5-(2-amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)-benzonitrile. Crude product was put on a previously conditioned SCX column (5 g). The column was washed with MeOH (2×10 ml) and then with 2N NH3/MeOH (2×10 ml) to retrieve the product 5-(2-amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)-benzonitrile (245 mg, 0.797 mmol, yield=38%, purity=91%). [M+H]+=308.23 1H NMR (300 MHz, CDCl3) δ/ppm 2.79 (br. s., 2H), 2.94-3.07 (m, 2H), 7.21 (br. s., 2H), 7.49 (d, J=8.9 Hz, 1H), 7.54 (br. s., 1H), 7.90-8.05 (m, 1H), 8.38 (br. s., 1H)
Workup
- customwas irradiated in microwave Biotage Initiator at 200° C. for 20 min
- temperatureAfter cooling
- extractionextraction with EtOAc (3×15 ml)
- dry with materialdried over Na2SO4/MgSO4
- filtrationfiltered off
- customevaporated in vacuo
Sources & evidence
- ORD record
- ord-1383ced33e1d43fea12dd294cf78b0c0
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637536B2
Reaction notes
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