Hydrochloric Acid → 4-(4-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid

HRID 601849Notes

Reaction equation

[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][CH:7]2[C:14]3[CH:13]=[C:12]([C:15]([O:17]C)=[O:16])[N:11](S(C4C=CC(C)=CC=4)(=O)=O)[C:10]=3[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[OH-].[K+].[Li+].[OH-].Cl>C1COCC1.CO.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]2[C:14]3[CH:13]=[C:12]([C:15]([OH:17])=[O:16])[NH:11][C:10]=3[CH2:9][CH2:8]2)=[CH:29][CH:30]=1

Participants

Conditions

Temperature: 70 °C

Procedure

The title compound was synthesized from methyl 4-(4-fluorobenzyl)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate in two steps. First, the starting material's methyl ester was hydrolyzed according to General Procedure 7. In this case, 0.070 g (0.274 mmol) of starting ester and potassium hydroxide (10 M, 0.16 mL, 1.6 mmol) were used. The deprotected methyl ester (4-(4-fluorobenzyl)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid) (0.035 g, 0.13 mmol) was then dissolved in THF (3 mL) and MeOH (3 mL), and LiOH (0.055 g, 1.3 mmol) in H2O (3 mL) was added and the reaction stirred at 70° C. for 6 h. The reaction was diluted in 25 mL H2O and acidified to pH 2-3 with 1 N HCl, then extracted with 2×50 mL EtOAc. The organic layer was dried over Na2SO4, concentrated and purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-100% EtOAc/heptane to afford the title compound. 16 mg. 19F NMR δ ppm −102.42 (m, J=5.4) LCMS-MS (ESI−) 258.0 (M−H); HPLC (UV=98.52%), (ELSD=100%).

Workup

extractionextracted with 2×50 mL EtOAc
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated
custompurified by column chromatography (Isco CombiFlash)
washeluting with a gradient of 0-100% EtOAc/heptane

Sources & evidence

ORD record: ord-909a791f00404e01a28d16a7a788dc26
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07902252B2

Reaction notes

Loading…