Hydrochloric Acid → HCID 178524786, compound

HRID 338512Notes

Reaction equation

HRID 338512 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 1M 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, 1H), 8.02 (s, 1H), 7.59 (s, 1H), 7.41 (d, 2H), 7.34 (d, 2H), 4.53-4.50 (m, 1H), 3.67-3.65 (m, 1H), 2.55-2.43 (m, 4H).

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-b7b71485b1d94eb0bfb381581bb745f9
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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