1-chloro-4-(cyclopropyloxy)isoquinoline synthesis

Yield:1409964-36-8 32.7%

Reaction Conditions:

with caesium carbonate in N,N-dimethyl-formamide at 145; for 18 h;Sealed tube;

Steps:

1 Preparation of 1-chloro-4-cyclopropoxyisoquinoline

To a solution of 1-chloroisoquinolin-4-ol (1.0 g, 55.7 mmol) in DMF (20 m) was added Cs₂CO₃(2.72 g, 8.35 mmol) followed by cyclopropylbromide (6.74 g, 55.7 mmol) at room temperature. The reaction vessel (Pressure tube) was sealed and heated at 145° C. for 18 h. The reaction mass was diluted with water and extracted with ethyl acetate. The combined organic layer was dried over anhydrous Na₂SO₄and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography to get desired compound (0.4 g, 32.7%) as a yellow solid.¹H NMR (400 MHz, CDCl₃): δ ppm 8.22-8.24 (m, 2H), 8.14 (s, 1H), 8.14-8.12 (m, 1H), 7.74-7.67 (m, 2H), 4.00-3.95 (m, 1H), 0.92-0.90 (m, 4H); MS: MS m/z 220.0 (M⁺+1).

References:

US9527885,2016,B2 Location in patent:Page/Page column 562; 563