Water → Methyl 2-(isoquinolin-5-yl)acetate

Participants

Reaction Conditions

Reaction Steps

5-Allylisoquinoline (Preparation 6, Step 2; 169 mg, 1.0 mmol) in methylene chloride (2 mL), acetic acid (0.5 mL), and water (0.5 mL) was treated with dimethyl polyethylene glycol (Mn ca. 500, 95 uL, 100 mg, 0.2 mmol) in methylene chloride (1 mL) at 23° C. The mixture was cooled to 0° C. and powdered KMnO4 (521 mg, 3.3 mmol) was added portionwise, maintaining the temperature below 30° C. Following vigorous stirring for 18 h, the solvent was removed in vacuo and methanolic hydrogen chloride (10 mL, 1N) was added, and the mixture was refluxed for 4 h. The methanol was removed in vacuo, the residue was diluted with water, and the mixture was made basic with Na2CO3 (pH=9). The mixture was extracted with ethyl acetate, the resulting organic layer was washed with brine, was dried (MgSO4), was filtered, was concentrated in vacuo, and was purified by silica gel chromatography (2:1 hexanes—ethyl acetate) to afford isoquinolin-5-yl-acetic acid methyl ester; 1H NMR (400 MHz, CDCl3) δ9.28 (brs, 1H), 8.58 (d, J=6.2 Hz, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.80 (d, J=5.8 Hz, 1H), 7.66 (d, J=5.8 Hz, 1H), 7.59 (t, J=7.6 Hz, 1H), 4.06 (s, 2H), 370 (s, 3H), MS (AP/Cl): 202.1 (M+H)+. Note: An impurity of 5-isoquinolylcarboxaldehyde was present following silica gel chromatography (ca. 20%).

Provenance & Evidence