Hydrochloric Acid → Benzyl (3S)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate--hydrogen chloride (1/1)

HRID 478949Notes

Reaction equation

HRID 478949 reaction equation
[CH2:1]([O:8][C:9]([C@@H:11]1[CH2:20][C:19]2[C:14](=[CH:15][C:16]([O:23][CH3:24])=[C:17]([O:21][CH3:22])[CH:18]=2)[CH2:13][N:12]1C(OC(C)(C)C)=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:32].CC(O)C>C(OCC)(=O)C.C1(C)C=CC=CC=1>[ClH:32].[CH2:1]([O:8][C:9]([C@@H:11]1[CH2:20][C:19]2[C:14](=[CH:15][C:16]([O:23][CH3:24])=[C:17]([O:21][CH3:22])[CH:18]=2)[CH2:13][NH:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3776Isopropanol2×HCID 12108676HCID 12108676, compound

Product 1

HCID 13044265Benzyl (3S)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate--hydrogen chloride (1/1)Yield 99%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a suspension of crude (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-(tert-butyloxycarbonyl)-3-isoquinolinecarboxylic acid benzyl ester (example 5) (335 g, 0.7836 mol) in ethyl acetate (335 mL) and toluene (335 mL) was added 20% HCl solution in IPA (357 g, 1.959 mol) at 15-20° C. The reaction mixture then was heated to 40° C. over 1-2 h, and stirred at this temperature for 2 h. A 20% HCl solution in IPA (71.4 g, 0.3918 mol) was added, and the stirring was continued for another 2 h. The reaction mixture was cooled to 15-20° C., and stirred at this temperature. The mixture was filtered, and washed with ethyl acetate (2×670 mL). The white solids were dried under vacuum at 40° C. to give 278.6 g (99% yield, ee=98%) of (S)-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid benzyl ester, hydrochloride. 1H NMR (DMSO-d6) δ: 3.10 (dd, J=16.64, 10.74 Hz, 1H, CHHCHCOOH), 3.24 (dd, J=16.64, 5.10 Hz, 1H, CHHCHCOOH), 3.72 (s, 6H, OCH3), 4.23 (br s, 2H, CH2N), 4.58 (dd, J=10.74, 5.10 hz, 1H, CHCOOH), 5.27 (d, J=12.48 Hz, 1H, PhCHH), 5.33 (d, J=12.48 Hz, 1H, PhCHH), 6.85 (br s, 2H, PhH), 7.35-7.46 (m, 5H, PhHCH2), 10.19 (br s, 2H, NH.HCl).

Workup

  1. waitthe stirring was continued for another 2 h
  2. temperatureThe reaction mixture was cooled to 15-20° C.
  3. stirringstirred at this temperature
  4. filtrationThe mixture was filtered
  5. washwashed with ethyl acetate (2×670 mL)
  6. customThe white solids were dried under vacuum at 40° C.

Sources & evidence

ORD record
ord-de2ed44533d8449994baf3b5a27c2a5c
Source dataset
uspto-grants-2003_11
Patent number
US06642384B1

Reaction notes

Loading…