Methyl 4-(4-fluorobenzylidene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate → Methyl 4-(4-fluorobenzyl)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601810Notes

Reaction equation

HRID 601810 reaction equation
FC1C=CC(C[Mg]Cl)=CC=1.[F:11][C:12]1[CH:40]=[CH:39][C:15]([CH:16]=[C:17]2[C:24]3[CH:23]=[C:22]([C:25]([O:27][CH3:28])=[O:26])[N:21]([S:29]([C:32]4[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[C:20]=3[CH2:19][CH2:18]2)=[CH:14][CH:13]=1>[Pd]>[F:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:16][CH:17]2[C:24]3[CH:23]=[C:22]([C:25]([O:27][CH3:28])=[O:26])[N:21]([S:29]([C:32]4[CH:33]=[CH:34][C:35]([CH3:36])=[CH:37][CH:38]=4)(=[O:30])=[O:31])[C:20]=3[CH2:19][CH2:18]2)=[CH:39][CH:40]=1

Participants

4

Reactant 2

HCID 66874708Methyl 4-(4-fluorobenzylidene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 178505759HCID 178505759, compound

Product 1

HCID 59180148Methyl 4-(4-fluorobenzyl)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateYield 14%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

The title compound was synthesized from tosyl protected methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (methyl 4-oxo-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate) (0.60 g, 1.8 mmol) and 4-fluorobenzylmagnesium chloride (0.25M in THF, 52 mL, 13 mmol) according to General Procedure 3 to give exo olefin-containing methyl 4-(4-fluorobenzylidene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (as a mixture of cis/trans isomers), then hydrogenation according to General Procedure 6. In this example, Degussa type, 5% palladium on carbon (˜0.200 g, 0.2 mmol) was used, and the reaction placed under a hydrogen atmosphere in a Parr shaker (˜40 PSI) for 2 hours. Purification by column chromatography (Isco CombiFlash) eluting with a gradient of 0-50% EtOAc/heptane affording the title compound as white crystals: 0.070 g (14% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.05-2.15 (m, 1H), 2.44 (s, 3H), 2.55-2.65 (m, 1H), 2.70-2.85 (m, 2H), 3.08 (t, 1H), 3.20-3.35 (m, 1H), 3.71 (s, 3H), 6.49 (s, 1H), 6.95-7.00 (m, 2H), 7.10-7.15 (m, 1H), 7.30-7.35 (d, J=8.4 Hz, 2H), 7.87 (d, J=8.4 Hz, 1H).

Workup

  1. customto give
  2. additionas a mixture of cis/trans isomers), then hydrogenation
  3. customPurification by column chromatography (Isco CombiFlash)
  4. washeluting with a gradient of 0-50% EtOAc/heptane affording the title compound as white crystals

Sources & evidence

ORD record
ord-729b2df5f5524309a5dec0017f8e8346
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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