Potassium Carbonate → 6,7-Dimethoxy-2-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propyl]1,2,3,4-tetrahydroisoquinoline

HRID 1451023Notes

Reaction equation

HRID 1451023 reaction equation
[O:1]1[CH2:20][CH:2]1[CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:14]3[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=3[O:12][N:11]=2)[CH2:6][CH2:5]1.C([O-])([O-])=O.[K+].[K+].Cl.[CH3:28][O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][C:39]=1[O:40][CH3:41])[CH2:36][NH:35][CH2:34][CH2:33]2>C(O)(C)C>[CH3:28][O:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][C:39]=1[O:40][CH3:41])[CH2:36][N:35]([CH2:20][CH:2]([OH:1])[CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]3[C:14]4[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=4[O:12][N:11]=3)[CH2:6][CH2:5]1)[CH2:34][CH2:33]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 64560356,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochlorideHCID 15285697N-(2,3-epoxypropyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine

Product 1

HCID 152856806,7-Dimethoxy-2-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propyl]1,2,3,4-tetrahydroisoquinolineYield 11%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A stirred mixture of 1-(2,3-epoxypropyl)-4-(6-fluoro-1,2-benzisoxazol-3yl)piperidine (3.2 g, 11.6 mmol), K2CO3 (2 gm, 1.25 eq) and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3.3 g, 1.25 eq) in isopropyl alcohol (200 ml) was heated at reflux for 6 hours. The mixture was cooled and filtered. The solvent was removed to about 50 ml and the solution was allowed to stand overnight. Crystals (0.6 g) formed and were collected. The mother liquor was concentrated to a white solid. Recrystallization twice from ethanol yielded the product (1.95 g, m.p. 153°-154° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 6 hours
  3. temperatureThe mixture was cooled
  4. filtrationfiltered
  5. customThe solvent was removed to about 50 ml

Sources & evidence

ORD record
ord-66092b1090d542e2a3518ccb9cdc2744
Source dataset
uspto-grants-1997_02
Patent number
US05602158

Reaction notes

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