Hydrochloric Acid → (+/-)-6-chloro-5-(4-{[trans-2-hydroxycyclopentyl]oxy}phenyl)-1H-indole-3-carboxylic acid
Reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([O:21][C@@H:22]2[CH2:26][CH2:25][CH2:24][C@H:23]2[OH:27])=[CH:17][CH:16]=1.[OH-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([O:21][C@@H:22]2[CH2:26][CH2:25][CH2:24][C@H:23]2[OH:27])=[CH:19][CH:20]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 75 °C
Procedure
A solution of (±)-methyl 6-chloro-5-(4-{[trans-2-hydroxycyclopentyl]oxy}phenyl)-1H-indole-3-carboxylate (32 mg, 0.083 mmol) in methanol (0.845 mL) was treated with 1 N aqueous sodium hydroxide (0.291 mL, 0.291 mmol). The solution was heated to 75° C. in a sealed vial for 24 hours. The cooled reaction mixture was poured into 0.3 N HCl (7 mL) and extracted with ethyl acetate (3×5 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The crude product was purified using reverse-phase chromatography to give the title compound. MS (ES−) 370.0 (M−H)−. Retention time: 1.66 min; Waters Xbridge dC18 5 μm 4.6×50 mm, 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. (0.03% NH4OH). Flow: 2.0 ml/min.
Workup
- customThe cooled reaction mixture
- extractionextracted with ethyl acetate (3×5 mL)
- dry with materialThe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- customevaporated
- customThe crude product was purified
Sources & evidence
- ORD record
- ord-dad3cf3f7c2f4b0f84bbcc54f21c5111
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394285B2
Reaction notes
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