Ethylene Glycol → 1-(2-Chlorophenyl)-4-[2-(isochroman-1-yl)ethyl]piperazine hydrochloride

HRID 1417793Notes

Reaction equation

HRID 1417793 reaction equation
[Cl:1][CH2:2][CH2:3][CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][O:5]1.Cl.Cl.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C(N(C(C)C)CC)(C)C.C(O)CO>CO>[ClH:1].[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:28][CH2:27][N:26]([CH2:2][CH2:3][CH:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH2:7][CH2:6][O:5]2)[CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 81531DiisopropylethylamineHCID 30186831-(2-Chlorophenyl)piperazine dihydrochlorideHCID 106079661-(2-Chloroethyl)isochroman

Product 1

HCID 703402871-(2-Chlorophenyl)-4-[2-(isochroman-1-yl)ethyl]piperazine hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A mixture of 1-(2-chloroethyl)isochroman (LXIV, PREPARATION 2, 0.497 g, 2.53 mmol), 1-(2-chlorophenyl)piperazine dihydrochloride (XI, 0.952 g, 3.79 mmol), diisopropylethylamine (1.76 ml, 10.1 mmol) and ethylene glycol (5 ml) is heated at 100° for 16 hr. After cooling, the mixture is partitioned between ethyl acetate and saline. The organic phase is dried over magnesium sulfate, concentrated, and the residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98) to give a material which is taken up in several mls of methanol. Methanol saturated with hydrochloric gas (6 ml) is added. After standing for several minutes, the mixture is concentrated under reduced pressure. Several mls of methanol are added back, followed by ether. The resulting solid is collected, washed with ether, and dried under vacuum to give the title compound; mp 197°-198°; MS ((m/z)) 356; IR (mineral oil) 1093, 1481, 743, 2436 and 2426 cm-1.

Workup

  1. temperatureis heated at 100° for 16 hr
  2. temperatureAfter cooling
  3. customthe mixture is partitioned between ethyl acetate and saline
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. concentrationconcentrated
  6. customthe residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98)
  7. customto give a material which
  8. waitAfter standing for several minutes
  9. concentrationthe mixture is concentrated under reduced pressure
  10. additionSeveral mls of methanol are added back
  11. customThe resulting solid is collected
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-9130e31ccade4ec2a30d0c82a202a4f3
Source dataset
uspto-grants-1999_03
Patent number
US05877317

Reaction notes

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