Methanol → 6-p-Tolyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid

HRID 601926Notes

Reaction equation

HRID 601926 reaction equation
[C:1]1([CH3:20])[CH:6]=[CH:5][C:4]([CH:7]2[C:11]3[NH:12][C:13]([C:15]([O:17]CC)=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[OH-].[Na+].CO>C1COCC1>[C:1]1([CH3:20])[CH:2]=[CH:3][C:4]([CH:7]2[C:11]3[NH:12][C:13]([C:15]([OH:17])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8]2)=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 59180248Ethyl 6-p-tolyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Product 1

HCID 591800886-p-Tolyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acidYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was synthesized from ethyl 6-p-tolyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.1423 g, 0.56 mmol, 1 equiv) and sodium hydroxide (1.4 mL, 14 mmol, 10M, 25 equiv), according to General Procedure 7. A 4-5:1 mixture of methanol (MeOH) and THF (5-6 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 40% methanol and increasing to 100% over 7 minutes) afforded the title compound (68.9 mg, 51%) with purity by HPLC of 97.9% (UV). LCMS m/e 240.2 (M−H). 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.17-2.26 (m, 1H), 2.29 (s, 3H), 2.62 (ddd, J=14.43, 6.06, 5.84 Hz, 1H), 2.68-2.77 (m, 1H), 2.85-2.96 (m, J=8.63, 8.49, 8.49, 4.20 Hz, 1H), 4.21 (dd, J=8.47, 5.42 Hz, 1H), 6.66 (s, 1H), 6.94-7.03 (m, 2H), 7.09 (d, J=7.91 Hz, 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-7b542b09c8f148e4b87c435273c1a3b1
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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