Reaction #42906

Reaction equation

HCl

EtOAc

1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid ethyl ester

LiOH—H2O

→

1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid

Yield 96.0%

Solvents

water

THF

H2O

Conditions

Workup

1. 1
   workup.WAITat then at room temperature for 18 hours
2. 2
   OtherThe layers were then separated
3. 3
   Extractionthe aqueous phase was extracted with EtOAc
4. 4
   WashThe combined organic layers were then washed with brine
5. 5
   Dryingdried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   OtherThe solvent was removed under reduced pressure

Procedure

To a solution of 1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid ethyl ester (520 mg, 1.34 mmol) in THF (10 ml) and H2O (10 ml) under nitrogen, LiOH—H2O (95 mg, 2.3 mmol) was added. The reaction was stirred at 50° C. for 3.5 hours and at then at room temperature for 18 hours. EtOAc and water were then added and the pH was adjusted to 5 by dropwise addition of 6N HCl. The layers were then separated and the aqueous phase was extracted with EtOAc. The combined organic layers were then washed with brine, dried over magnesium sulfate and filtered. The solvent was removed under reduced pressure to give 1-(tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid as a solid (464 mg, 96%). H1-NMR (DMSO): δ, 8.84 (s, 1H), 7.96 (s, 1H), 6.91 (t, 1H, J=5.4 Hz), 6.77 (s, 1H), 4.80 (d, 2H, J=5.43 Hz), 3.95 and 3.88 (s, 3H each), 1.36 (s, 9H).

Source