Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1) → N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]morpholine

HRID 1900420Notes

Reaction equation

HRID 1900420 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.Cl.Cl[CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1>C(#N)C.C(Cl)Cl>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 2

HCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 21960100N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]morpholine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), 2-chloroethyl morpholine hydrochloride (4.46 g, 29.7 mmol) and K2O3 (7.3 g, 2.2 eq) in acetonitrile (60 ml) was heated at reflux for 24 hours. The crude mixture was diluted with DCM and filtered. The solvent was concentrated to an oil (~7.1 g). Purification on a silica gel column (55 g, SiO2, eluted with MeOH:DCM) yielded a solid product weighing 4 g. Recrystallization from hot ethanol yielded 2.1 g (48%), m.p.=131°-132° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 24 hours
  3. filtrationfiltered
  4. concentrationThe solvent was concentrated to an oil (~7.1 g)
  5. customPurification
  6. washon a silica gel column (55 g, SiO2, eluted with MeOH:DCM)
  7. customyielded a solid product
  8. customRecrystallization from hot ethanol
  9. customyielded 2.1 g (48%), m.p.=131°-132° C.

Sources & evidence

ORD record
ord-a189f537b6c34f298c2941d4063e3798
Source dataset
uspto-grants-1996_11
Patent number
US05574032

Reaction notes

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