Hydrochloric Acid → 4-{2-[2-(2-Amino-ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]-propyl}-benzoic acid

HRID 730950Notes

Reaction equation

HRID 730950 reaction equation
C([NH:4][CH2:5][CH2:6][C:7]1[N:8]([CH:29]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:9]2[C:14]([C:15]=1[CH2:16][CH2:17]CC1C=CC(C(O)=O)=CC=1)=[CH:13][C:12](Cl)=[CH:11][CH:10]=2)(=O)C.[OH-:42].[K+].[ClH:44].[CH3:45][OH:46]>O>[NH2:4][CH2:5][CH2:6][C:7]1[N:8]([CH:29]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:9]2[C:14]([C:15]=1[CH:16]([CH3:17])[CH2:15][C:14]1[CH:9]=[CH:10][C:11]([C:45]([OH:46])=[O:42])=[CH:12][CH:13]=1)=[CH:13][C:12]([Cl:44])=[CH:11][CH:10]=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887Methanol2×HCID 14797Potassium HydroxideHCID 113874774-{3-[2-(2-Acetylamino-ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]-propyl}-benzoic acid

Product 1

HCID 574411164-{2-[2-(2-Amino-ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]-propyl}-benzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-{3-[2-(2-Acetylamino-ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]-propyl}-benzoic acid (175 g, 0.310 mol) is added to a stirred solution of methanol (700 mL), water (175 mL) and potassium hydroxide (385 g, 5.83 mol). The mixture is wormed to 86° C. for 16 h-24 h. The reaction is complete when the product/starting material ratio is greater than 99/1 by HPLC. The following addition steps should maintain the reaction mixture at an internal temperature of 60° C.-65° C. Methanol (1500 mL) is added to the reaction mixture. Concentrated HCl (480 mL) is added over a 30 min to the reaction mixture, neutralizing the mixture to a pH of 5 to 7. Precipitation occurs and the reaction mixture becomes lighter. Water (2.5 L) is added over 30 min and stir the reaction mixture for 30 min at 60° C.-65° C. The reaction mixture is cooled to room temperature. The product is collected by filtration and washed with warm water (3×250 mL, 50° C.-60° C.) and cold methanol (250 mL, 0° C.-5° C.). Drying the product in vacuo at 60° C.-70° C. gives 152 g (94%, 95.0% by HPLC) of 4-{2-[2-(2-Amino-ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]-propyl}-benzoic acid.

Workup

  1. waitThe mixture is wormed to 86° C. for 16 h-24 h
  2. additionThe following addition steps
  3. temperatureshould maintain the reaction mixture at an internal temperature of 60° C.-65° C
  4. customPrecipitation
  5. additionWater (2.5 L) is added over 30 min
  6. filtrationThe product is collected by filtration
  7. washwashed with warm water (3×250 mL, 50° C.-60° C.) and cold methanol (250 mL, 0° C.-5° C.)
  8. customDrying the product in vacuo at 60° C.-70° C.

Sources & evidence

ORD record
ord-46dabc5940ce4f5c9df4dfcf95362063
Source dataset
uspto-grants-2009_09
Patent number
US07582771B2

Reaction notes

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