Methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate → Methyl 4-(3-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601815Notes

Reaction equation

HRID 601815 reaction equation
O=[C:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1.[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[CH2:18][Mg]Cl.ClC1C=C(C=CC=1F)/C=C1\CCC2NC(C(OC)=O)=CC\1=2>[Pd]>[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[CH2:18][CH:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 59180145Methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 67269034(E)-methyl 4-(3-chloro-4-fluorobenzylidene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 178505696HCID 178505696, compound

Product 1

HCID 59180099Methyl 4-(3-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

The title compound was synthesized in two steps. First, methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.50 g, 2.79 mmol) was reacted with 3-fluorobenzylmagnesium chloride (0.25 M in diethyl ether, 52 mL, 13 mmol) according to General Procedure 3. The resulting exo-olefin ((E)-methyl 4-(3-fluorobenzylidene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate) was then converted to the title compound by hydrogenation according to General Procedure 6. In this example, Degussa type, 5% palladium on carbon (0.100 g, 0.1 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 0-40% EtOAc/heptane afforded the title compound. 0.075 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.03-2.11 (m, 1H), 2.47-2.56 (m, 1H), 2.59-2.73 (m, 2H), 2.78 (d, J=7.4 Hz, 2H), 3.24-3.32 (m, 1H), 3.81 (s, 3H), 6.39 (d, J=1.7 Hz, 1H), 6.90-7.00 (m, 3H), 7.20-7.35 (m, 1H), 8.94 (br s, 1H).

Workup

  1. customThe title compound was synthesized in two steps
  2. customPurification by column chromatography (Isco CombiFlash)
  3. washeluting with a gradient of 0-40% EtOAc/heptane

Sources & evidence

ORD record
ord-951dfa28c97f495f82c84d866687f238
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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