Hydrochloric Acid → 1,2,3,4-Tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid hydrochloride

HRID 478950Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][N:8](C(OC(C)(C)C)=O)[C@H:7]([C:22]([OH:24])=[O:23])[CH2:6]2.[ClH:25]>CO>[ClH:25].[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][NH:8][C@H:7]([C:22]([OH:24])=[O:23])[CH2:6]2

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(tert-butyloxycarbonyl)-3-isoquinolinecarboxylic acid (example 3) (60 g, 0.17 mol) in methanol (300 mL) was added 3 N aqueous HCl (240 mL, 0.72 mol). The mixture was heated to 60° C. and stirred at 60° C. for 2 hrs. The clear reaction solution was evaporated under vacuum to 200 mL. The resulting white suspension was then cooled to 0-5° C. and stirred at 0-5° C., filtered, and rinsed with cold water (2×35 mL). The solid was dried under vacuum to give 42 g of (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid hydrochloride (yield 90.9%, ee>98%). 1H NMR (DMSO-d6) δ: 3.06 (dd, J=16.7, 10.8 Hz, 1H, CHHCHCOOH), 3.22 (dd, J=16.7, 4.7 Hz, 1H, CHHCHCOOH), 3.72, 3.73 (s, 6 H, OCH3), 4.21 (br s, 2H, CH2N), 4.32 (dd, J=10.8, 4.7 Hz, 1H, CHCOOH), 6.85, 6.87 (s, 2H, PhH), 10.12 (br s, 2H, NHHCl).

Workup

customThe clear reaction solution was evaporated under vacuum to 200 mL
temperatureThe resulting white suspension was then cooled to 0-5° C.
stirringstirred at 0-5° C.
filtrationfiltered
washrinsed with cold water (2×35 mL)
customThe solid was dried under vacuum

Sources & evidence

ORD record: ord-2ca35e56650b41119daef8bcfa7dc33e
Source dataset: uspto-grants-2003_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06642384B1

Reaction notes

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