Hydrochloric Acid → HCID 16115792, compound

HRID 730949Notes

Reaction equation

HRID 730949 reaction equation
[OH-].[K+].C([NH:6][CH2:7][CH2:8][C:9]1[N:10]([CH:31]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:11]2[C:16]([C:17]=1[CH2:18][CH2:19][O:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)=[CH:15][C:14]([Cl:30])=[CH:13][CH:12]=2)(=O)C.Cl>O.CO>[NH2:6][CH2:7][CH2:8][C:9]1[N:10]([CH:31]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:11]2[C:16]([C:17]=1[CH2:18][CH2:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:28][CH:29]=1)=[CH:15][C:14]([Cl:30])=[CH:13][CH:12]=2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 69058931HCID 69058931, compound

Product 1

HCID 16115792HCID 16115792, compoundYield 96.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
86 °C

Procedure

Methanol (660 mL), water (165 mL) and potassium hydroxide (365 g, 5.53 mol) was combined with 4-{2-[2-(2-Acetylamino-ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]-ethoxy}-benzoic acid (165 g, 0.291 mol). The reaction mixture was stirred at 86° C. (gentle reflux) for 16-24 hours. The reaction mixture was cooled to 75° C. and methanol (1.5 L) was added keeping the internal temperature 50° C.-55° C. The reaction mixture was neutralized (pH 5-7) by adding concentrated HCl (450 mL) over 30 minutes maintaining 60° C.-65° C. The reaction mixture became thicker and lighter in color. Water (3 L) was added to the mixture over 30 minute maintaining 60° C.-65° C. The reaction mixture was cooled to 22° C.-28° C. The product was collected by vacuum filtration followed by waster wash (3×500 mL) and cold (0°-5° C.) methanol (2×300 mL). The product was dried to give the desired product (148 g, 96.5% purity, HPLC). 1HNMR (DMSO−d6): δ7.75 (d, 2H, J=8 Hz), 7.64 (d,1H, J=2 Hz), 7.30 (m, 5H), 7.17 (brs, 1H), 7.09 (d, 1H, J=2 Hz), 7.07 (s, 1H), 6.81 (dd, 1H, J=9 Hz, 2 Hz), 6.72 (d, 2H, J=9 Hz), 6.55 (d, 1H, J=9 Hz), 4.09 (br m, 2H), 3.16 (br m, 4H), 2.50 (br m, 2H).

Workup

  1. temperature(gentle reflux) for 16-24 hours
  2. temperatureThe reaction mixture was cooled to 75° C.
  3. customthe internal temperature 50° C.-55° C
  4. temperaturemaintaining 60° C.-65° C
  5. temperaturemaintaining 60° C.-65° C
  6. temperatureThe reaction mixture was cooled to 22° C.-28° C
  7. filtrationThe product was collected by vacuum filtration
  8. washwash (3×500 mL) and cold (0°-5° C.) methanol (2×300 mL)
  9. customThe product was dried

Sources & evidence

ORD record
ord-019e4f4510664fe794d9f4a41bf4f773
Source dataset
uspto-grants-2009_09
Patent number
US07582771B2

Reaction notes

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