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 1899577Notes

Reaction equation

HRID 1899577 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-3-yl)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-c2bd1301fe724593abef3bb9920851b7
Source dataset
uspto-grants-1996_11
Patent number
US05571828

Reaction notes

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