Toluene → HCID 12971684, compound

HRID 277500Notes

Reaction equation

HRID 277500 reaction equation
C1(C)C=CC=CC=1.[OH:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[CH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH2:30][CH2:31][CH3:32])[CH:27]=2)[CH:22]([C:33]2[CH:38]=[CH:37][C:36]3[O:39][CH2:40][O:41][C:35]=3[CH:34]=2)[CH:21]1[C:42]([OH:44])=[O:43].[CH2:45]([NH2:48])[CH2:46][NH2:47]>CC(O)C>[CH2:45]([NH2:48])[CH2:46][NH2:47].[OH:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[C@@H:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH2:30][CH2:31][CH3:32])[CH:27]=2)[C@H:22]([C:33]2[CH:38]=[CH:37][C:36]3[O:39][CH2:40][O:41][C:35]=3[CH:34]=2)[C@H:21]1[C:42]([OH:44])=[O:43]

Participants

5

Reactant 3

HCID 1140TolueneHCID 3301EthylenediamineHCID 18427691HCID 18427691, compound

Product 1

HCID 12971684HCID 12971684, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A toluene solution of (+)(1S,2R,3S)]-3-[2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl]-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid (868.8 g @ 11.2% wt/wt, 192.5 mmol) was concentrated under reduced pressure to a volume of approximately 200 mL. Distillation was discontinued and 2-propanol (500 mL) added to the concentrate. The organic solution was concentrated again under reduced pressure to a volume of approximately 200 mL. Distillation was discontinued and 2-propanol (500 mL) added to the concentrate. The resulting solution in 2-propanol was allowed to stir at ambient temperature for approximately 15 minutes to obtain a homogeneous mixture then diluted with an additional 1000 mL of 2-propanol. The resulting solution was heated to approximately 60° C. over a period of 15-20 minutes under a gentle purge of nitrogen. Heating was discontinued and ethylene diamine (11.6 g, 99.5 +%. 192.5 mmol) was added. The reaction mixture was cooled to 30-35° C. over a period of 4 hours. As the solution cooled to 57° C., precipitation of the title compound occurred. The resulting slurry was stirred at ambient temperature for approximately 12 hours then cooled to 0° C. an additional 3 hours before isolation of the title compound via filtration. The product was washed with 3 portions of 2-propanol (300 mL) followed by hexane's (600 mL) chilled to 0-5° C. The product was dried in the vacuum oven for approximately 16 hours at 20-25° C. to afford 91.6 (87%) of the title compound.

Workup

  1. distillationDistillation
  2. addition2-propanol (500 mL) added to the concentrate
  3. concentrationThe organic solution was concentrated again under reduced pressure to a volume of approximately 200 mL
  4. distillationDistillation
  5. addition2-propanol (500 mL) added to the concentrate
  6. customto obtain a homogeneous mixture
  7. temperatureThe resulting solution was heated to approximately 60° C. over a period of 15-20 minutes under
  8. customa gentle purge of nitrogen
  9. temperatureHeating
  10. temperatureThe reaction mixture was cooled to 30-35° C. over a period of 4 hours
  11. temperatureAs the solution cooled to 57° C.
  12. customprecipitation of the title compound
  13. stirringThe resulting slurry was stirred at ambient temperature for approximately 12 hours
  14. temperaturethen cooled to 0° C. an additional 3 hours before isolation of the title compound via filtration
  15. washThe product was washed with 3 portions of 2-propanol (300 mL)
  16. temperaturechilled to 0-5° C
  17. customThe product was dried in the vacuum oven for approximately 16 hours at 20-25° C.

Sources & evidence

ORD record
ord-6232ac5af5be49e9a1b7713a7cbe75fd
Source dataset
uspto-grants-2002_03
Patent number
US06355813B1

Reaction notes

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