Isopropanol → N-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propyl]-1,2,3,4-tetrahydroisoquinoline difumarate

HRID 1533410Notes

Reaction equation

HRID 1533410 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[CH2:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][CH2:19][NH:18]1.[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31].[CH:35]([OH:38])([CH3:37])[CH3:36]>C(O)C>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31].[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]/[C:30]([OH:32])=[O:31].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:36][CH:35]([OH:38])[CH2:37][N:18]4[CH2:19][CH2:20][C:21]5[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=5)[CH2:17]4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 70461,2,3,4-TetrahydroisoquinolineHCID 444972Fumaric AcidHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 67071117N-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propyl]-1,2,3,4-tetrahydroisoquinoline difumarate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of N-13-(2,3-epoxy)propyl]-4-(6-fluoro-1,2-benzisoxaz-3-yl)piperidine (3.56 g, 12.9 mmol) and 1,2,3,4-tetrahydroisoquinoline (2.06 g, 15.4 mmol) in isopropyl alcohol (150 ml) was heated at reflux for 4 hours. At the end of the reaction, the solvent was removed. The residual oil was purified by flash chromatography over a silica gel column (SiO2, 45 g, eluted with 1% CH3OH: 99% methylene chloride). The product thus purified as a light oil, weighed 4.15 g. The oil was treated with a solution of fumaric acid (1.98 gm, 17 mmol) in ethanol. The white crystals so obtained were recrystallized in a large volume of hot ethanol (˜150 ml). The recrystallized crystals weighed 2.75 g, m.p. 179-181° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. customAt the end of the reaction
  4. customthe solvent was removed
  5. customThe residual oil was purified by flash chromatography over a silica gel column (SiO2, 45 g, eluted with 1% CH3OH: 99% methylene chloride)
  6. customThe product thus purified as a light oil
  7. customThe white crystals so obtained
  8. customwere recrystallized in a large volume of hot ethanol (˜150 ml)

Sources & evidence

ORD record
ord-76836f4f19b64a18888fb212a0a9ed01
Source dataset
uspto-grants-2001_03
Patent number
US06207680B1

Reaction notes

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