Hydrochloric Acid → 1-(Tert-butoxycarbonylamino-methyl)-6,8-dimethoxy-isoquinoline-4-carboxylic acid

HRID 14628

Reaction equation

C([O:3][C:4]([C:6]1[C:15]2[C:10](=[C:11]([O:18][CH3:19])[CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9]([CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[N:8][CH:7]=1)=[O:5])C.O[Li].O.CCOC(C)=O.Cl>C1COCC1.O>[C:25]([O:24][C:22]([NH:21][CH2:20][C:9]1[C:10]2[C:15](=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[O:18][CH3:19])[C:6]([C:4]([OH:5])=[O:3])=[CH:7][N:8]=1)=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

Conditions

Temperature: 50 °C

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).

Workup

waitat then at room temperature for 18 hours
customThe layers were then separated
extractionthe aqueous phase was extracted with EtOAc
washThe combined organic layers were then washed with brine
dry with materialdried over magnesium sulfate
filtrationfiltered
customThe solvent was removed under reduced pressure

Sources & evidence

ORD record: ord-0ebda1cd5a5b46b19dc8d2e133fb3bbe
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07732446B1

Linked notes

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