2-METHOXY-4-(TRIFLUOROMETHYL)BENZYLAMINE synthesis

Yield:-

Reaction Conditions:

with lithium aluminium tetrahydride at 0 - 20; for 12 h;

Steps:

2 General Procedure for synthesis of isopropylether-pyrrolidone derivatives 3a - 3d:

General procedure: A solution of 2-fluoro-4-(trifluoromethyl)benzonitrile 1 (5.3 mmol) in ROH (150 mmol) was added slowly to NaH (26.5 mmol) at 0 - 5 °C. The resulting mixture was then warmed up to room temperature for 12 h. Then saturated saline solution (10 mL) was added slowly and the reaction mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic extracts were washed with saturated saline solution (20 mL), dried over anhydrous Na₂SO₄, concentrated and purified by flash chromatography (Ethyl Acetate/Petroleum Ether = 1:3, v/v) to afford 2a - 2d. A solution of 2a - 2d in 40 mL ether was added slowly to LiAlH₄ (8.6 mmol) at 0-5 °C. The resulting mixture was then warmed up to room temperature for 12 h. After anhydrous Na₂SO₄ (2.00 g) was added slowly, the mixture filtrated and washed with ethyl acetate (120 mL). The organic layer was dried over anhydrous Na₂SO₄, concentrated to afford 3a - 3d used in next step without purification.

References:

Li, Jin;Wu, Yuelin;Guo, Zizhao;Zhuang, Chunlin;Yao, Jianzhong;Dong, Guoqiang;Yu, Zhiliang;Min, Xiao;Wang, Shengzheng;Liu, Yang;Wu, Shanchao;Zhu, Shiping;Sheng, Chunquan;Miao, Zhenyuan;Zhang, Wannian [Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,# 12,p. 2648 - 2650] Location in patent:supporting information