Dimethylformamide → 1-[3-[4-(4,5-dihydro-2-oxazolyl)phenoxy]propyl]-4-(phenylmethyl)piperazine (Z)-2-butenedioate

HRID 981607Notes

Reaction equation

HRID 981607 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[O:26][CH2:27][CH2:28][N:29]=2)=[CH:21][CH:20]=1.[C:30](=[O:33])([O-:32])[O-].[Na+].[Na+].CN(C)C=[O:39]>>[C:25]([OH:26])(=[O:39])/[CH:22]=[CH:23]\[C:30]([OH:32])=[O:33].[O:26]1[CH2:27][CH2:28][N:29]=[C:25]1[C:22]1[CH:23]=[CH:24][C:19]([O:18][CH2:17][CH2:16][CH2:15][N:11]2[CH2:10][CH2:9][N:8]([CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:13][CH2:12]2)=[CH:20][CH:21]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 759941-BenzylpiperazineHCID 149891772-[4-(3-Chloropropoxy)phenyl]-4,5-dihydrooxazole

Product 1

HCID 1317167941-[3-[4-(4,5-dihydro-2-oxazolyl)phenoxy]propyl]-4-(phenylmethyl)piperazine (Z)-2-butenedioateYield 24.5%

Procedure

A mixture of 47.6 parts of 1-(phenylmethyl)piperazine, 65,8 parts of 2-[4-(3-chloropropoxy)phenyl]-4,5-dihydrooxazole, 28.6 parts of sodium carbonate and 282 parts of N,N-dimethylformamide was stirred over weekend at 60°~65° C. The reaction mixture was evaporated and the residue was taken up in water. The product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the (Z)-2-butenedioate salt in methanol. The salt was filtered off, washed with methanol and 2,2'-oxybispropane and crystallized from methanol. The product was filtered off, washed with water and dried at 70° C., yielding 40.6 parts (24.5%) of 1-[3-[4-(4,5-dihydro-2-oxazolyl)phenoxy]propyl]-4-(phenylmethyl)piperazine (Z)-2-butenedioate(1:2); mp. 178.0° C. (int. 15).

Workup

  1. customThe reaction mixture was evaporated
  2. extractionThe product was extracted with dichloromethane
  3. customThe extract was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. filtrationThe salt was filtered off
  11. washwashed with methanol and 2,2'-oxybispropane
  12. customcrystallized from methanol
  13. filtrationThe product was filtered off
  14. washwashed with water
  15. customdried at 70° C.

Sources & evidence

ORD record
ord-a8880fbd0ec74cb88f98d225a5246625
Source dataset
uspto-grants-1991_02
Patent number
US04992433

Reaction notes

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