Toluene → HCID 191618, compound

HRID 1380637Notes

Reaction equation

HRID 1380637 reaction equation
[O:1]=[C:2]1[CH:10](Br)[CH2:9][C:5]2[N:6]=[CH:7][S:8][C:4]=2[CH2:3]1.[CH:12]([NH:15][CH2:16][CH:17]([OH:20])[CH2:18]O)([CH3:14])[CH3:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>O.C(OCC)(=O)C>[CH:12]([NH:15][CH2:16][CH:17]([OH:20])[CH2:18][O:1][C:2]1[CH:10]=[CH:9][C:5]2[N:6]=[CH:7][S:8][C:4]=2[CH:3]=1)([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 1140TolueneHCID 1108573-Isopropylamino-1,2-propanediolHCID 521998p-Toluenesulfonic acid monohydrateHCID 13590069HCID 13590069, compound

Product 1

HCID 191618HCID 191618, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-oxo-5-bromo-4,5,6,7-tetrahydrobenzothiazole (100 parts), 3-isopropylamino-1,2-propanediol (67 parts), p-toluenesulfonic acid monohydrate (99 parts) and toluene (1550 parts) is heated under reflux for 21 hours while drying the refluxing azeotropic mixture according to the method described in Example I. After cooling, the reaction mixture is adjusted to pH 9 by adding aqueous 2.5N-sodium hydroxide and formed organic layer is separated. The organic layer is washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The remaining 4'-isopropylaminomethyl-5-bromo-4,5,6,7-tetrahydrobenzothiazole-6-spiro-2'-[1,3]-dioxolane (156 parts) is dissolved in piperidine (1560 parts), and stirred for 49 hours on an oil bath heated at 95° to 100° C. The reaction mixture is concentrated under reduced pressure to leave residue which is mixed with ethyl acetate and water, shaken and fractionated to separate formed organic layer. The organic layer is washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Residue (172 parts) is recrystallized from ethanol-hydrochloric acid giving 6-(3-isopropylamino-2-hydroxypropoxy)benzothiazole (65 parts) in 57% yield. mp. 132°-134° C. (hydrochloride trihydrate).

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 21 hours
  3. customwhile drying the refluxing azeotropic mixture
  4. temperatureAfter cooling
  5. additionby adding aqueous 2.5N-sodium hydroxide
  6. customformed organic layer
  7. customis separated
  8. washThe organic layer is washed with water
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe remaining 4'-isopropylaminomethyl-5-bromo-4,5,6,7-tetrahydrobenzothiazole-6-spiro-2'-[1,3]-dioxolane (156 parts) is dissolved in piperidine (1560 parts)
  12. temperatureheated at 95° to 100° C
  13. concentrationThe reaction mixture is concentrated under reduced pressure
  14. customto leave residue which
  15. stirringshaken
  16. customto separate
  17. customformed organic layer
  18. washThe organic layer is washed with water
  19. dry with materialdried over anhydrous sodium sulfate
  20. concentrationconcentrated under reduced pressure
  21. customResidue (172 parts) is recrystallized from ethanol-hydrochloric acid

Sources & evidence

ORD record
ord-0d0ca01e43324118909a0eae512e2bc3
Source dataset
uspto-grants-1986_04
Patent number
US04582905

Reaction notes

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