1-Butanol → 1-[4-[2-(2-Hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1,4]thiazepine

HRID 2246817Notes

Reaction equation

HRID 2246817 reaction equation
Cl[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[S:6][C:5]2[CH:13]=[CH:14][CH:15]=[CH:16][C:4]=2[N:3]=1.OCCO[CH:21]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)[CH3:22].[C:29](=[O:32])([O-])[O-].[K+].[K+].[I-].[K+].Cl.[CH2:38]([OH:42])CCC>>[OH:42][CH2:38][CH2:29][O:32][CH2:22][CH2:21][N:23]1[CH2:24][CH2:25][N:26]([C:9]2[C:8]3[CH:2]=[N:3][C:4]4[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=4[S:6][C:7]=3[CH:12]=[CH:11][CH:10]=2)[CH2:27][CH2:28]1

Participants

7

Reactant 6

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 1058648111-Chlorodibenzo(b,f)(1,4)thiazepineHCID 193588281-(2-Hydroxyethoxy)ethylpiperazine

Product 1

HCID 536923251-[4-[2-(2-Hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1,4]thiazepine

Procedure

A 2 liter round bottom flask equipped with stirring rod, thermo pocket, reflux condenser and nitrogen inlet was charged with 50 gm (0.2 moles) of 11-chlorodibenzo[b,f][1,4]-thiazepine and 500 cc n-butanol and the mixture was stirred for 15 min. at room temperature. The resulting solution was combined with 39 gm (0.22 mole) of 1-(2-hydroxyethoxy)ethylpiperazine, 56.2 gm (0.40 mole) of potassium carbonate and 16.89 gm (0.10 mole) of potassium iodide. The reaction mixture was heated at gentle reflux for 12 hrs and a sample of the reaction mixture was analyzed by HPLC. The analysis revealed that starting material remains less than 1%. The reaction mixture was cooled to room temperature and treated with 1000 cc 1N hydrochloric acid solution to get a pH in between 1 to 2. The layers (aqueous and nonaqueous reaction solvent) were separated and the aqueous layer was extracted with 500 cc toluene and pH was adjusted between 8 to 9 by addition of sodium carbonate. The layers were separated and aqueous layer was again extracted with 500 cc toluene. The organic layers (n-butanol and toluene) were combined and washed with 2×500 cc of water. The solvent was distilled under vacuum at 70 to 80° C. to afford 47.5 gm oil. HPLC area %: 98.9

Workup

  1. customA 2 liter round bottom flask equipped
  2. temperaturethermo pocket, reflux condenser and nitrogen inlet
  3. stirringthe mixture was stirred for 15 min. at room temperature
  4. temperatureThe reaction mixture was heated
  5. temperatureat gentle reflux for 12 hrs
  6. customto get a pH in between 1 to 2
  7. customThe layers (aqueous and nonaqueous reaction solvent) were separated
  8. extractionthe aqueous layer was extracted with 500 cc toluene and pH
  9. additionwas adjusted between 8 to 9 by addition of sodium carbonate
  10. customThe layers were separated
  11. extractionaqueous layer was again extracted with 500 cc toluene
  12. washwashed with 2×500 cc of water
  13. distillationThe solvent was distilled under vacuum at 70 to 80° C.

Sources & evidence

ORD record
ord-177539cae9264037a72b3c89b1570bec
Source dataset
uspto-grants-2010_03
Patent number
US07687622B2

Reaction notes

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