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

HRID 601813Notes

Reaction equation

HRID 601813 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.[Cl:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:18][Mg]Cl.FC1C=C(F)C=CC=1/C=C1\CCC2NC(C(OC)=O)=CC\1=2>>[Cl:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[F:24])[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

4

Reactant 3

HCID 59180145Methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 67269530(E)-methyl 4-(2,4-difluorobenzylidene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 178505760HCID 178505760, compound

Product 1

HCID 59180141Methyl 4-(3-chloro-4-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

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, 2.8 mmol) was reacted with 3-chloro-4-fluorobenzylmagnesium chloride (0.25 M in diethyl ether, 28 mL, 7 mmol) according to General Procedure 3. The resulting exo-olefin ((E)-methyl 4-(3-chloro-4-fluorobenzylidene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate) was then converted to the title compound by hydrogenation according to General Procedure 6 (with Pt2O). The crude product was purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-50% EtOAc/heptane to afford the title compound. 0.034 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.00-2.16 (m, 1H) 2.50-2.64 (m, 1H) 2.64-2.71 (m, 2H) 2.75 (d, J=7.37 Hz, 2H) 3.16-3.38 (m, 1H) 3.82 (s, 3H) 6.37 (d, J=1.66 Hz, 1H) 6.97-7.11 (m, 2H) 7.23 (dd, J=7.13, 2.00 Hz, 1H) 8.85 (br. s, 1H)).

Workup

  1. customThe title compound was synthesized in two steps
  2. customThe crude product was purified by column chromatography (Isco CombiFlash)
  3. washeluting with a gradient of 0-50% EtOAc/heptane

Sources & evidence

ORD record
ord-396d7d28068941ed97fd041297e14d27
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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