Methanol → 6-(4-Chlorophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid

HRID 601923Notes

Reaction equation

HRID 601923 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:12]3[NH:13][C:14]([C:16]([O:18]CC)=[O:17])=[CH:15][C:11]=3[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH-].[Na+].CO>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[C:12]3[NH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][C:11]=3[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 59180229HCID 59180229, compound

Product 1

HCID 591801666-(4-Chlorophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acidYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was synthesized from ethyl 6-(4-chlorophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.0907 g, 0.34 mmol, 1 equiv) and sodium hydroxide (0.86 mL, 8.6 mmol, 10 M, 25 equiv), according to General Procedure 7. A 2-3:1 mixture of methanol (MeOH) and THF (3-4 mL) was used. The resulting product was purified by preparative HPLC using the Chromeleon purification system. A 0.1% formic acid/1% acetonitrile mixture in water (aqueous phase) and methanol (no modifier added—organic phase) using a 50 mm Dynamax HPLC C-18 column at 28 mL/min (initial gradient of 50% methanol and increasing to 100% over 7 minutes) afforded the title compound (48.3 mg, 59%) with purity by HPLC of 94.1% (UV). LCMS m/e 260.2 (M−H). 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.16-2.30 (m, J=13.14, 8.19, 5.37, 5.37 Hz, 1H), 2.56-2.67 (m, 1H), 2.68-2.79 (m, 1H), 2.86-3.01 (m, 1H), 4.26 (dd, J=8.48, 5.28 Hz, 1H), 6.65 (s, 1H), 7.05-7.13 (m, 2H), 7.22-7.31 (m, 2H).

Workup

  1. customThe resulting product was purified by preparative HPLC
  2. customthe Chromeleon purification system
  3. temperatureincreasing to 100% over 7 minutes)

Sources & evidence

ORD record
ord-d0eecfba4d184391892d7f0d90d3db18
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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