Hydrochloric Acid → HCID 178524786, compound

HRID 1054856Notes

Reaction equation

HRID 1054856 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]([C@H:21]2[CH2:24][C@H:23]([OH:25])[CH2:22]2)=[CH:17][CH:16]=1.[OH-].[Na+].Cl>CO.O>[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]([C@H:21]2[CH2:24][C@H:23]([OH:25])[CH2:22]2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178498872HCID 178498872, compound

Product 1

HCID 178524786HCID 178524786, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

To a solution of methyl 6-chloro-5-[4-(trans-3-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylate (290 mg, 0.82 mmol) in methanol/water (20 mL, v/v=1/1) was added sodium hydroxide (326 mg, 8.17 mmol). The mixture was stirred at 90° C. for 5 hours. The mixture was then acidified with 1 M HCl to pH˜5. The resulting suspension was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by reverse phase HPLC to give the title compound (150 mg, 54%) as a white solid. MS (AP+) 342.0 (M+H)+: 1H NMR (500 MHz, CD3OD) δ 8.03 (s, 1 H), 8.02 (s, 1 H), 7.59 (s, 1 H), 7.41 (d, 2 H), 7.34 (d, 2 H), 4.53-4.50 (m, 1 H), 3.67-3.65 (m, 1 H), 2.55-2.43 (m, 4 H).

Workup

  1. extractionThe resulting suspension was extracted with dichloromethane
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-6f3e8739de7a45c5947d41f832dbaa0d
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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