Phenylboronic Acid → Methyl 4-(biphenyl-3-ylmethyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601830Notes

Reaction equation

HRID 601830 reaction equation
CC1C2C(=O)CCC=2N(S([C:13]2[CH:19]=[CH:18][C:16](C)=[CH:15][CH:14]=2)(=O)=O)C=1C(O)=O.O=[C:25]1[C:32]2[CH:31]=[C:30]([C:33]([O:35][CH3:36])=[O:34])[NH:29][C:28]=2[CH2:27][CH2:26]1.BrC1C=C(C=CC=1)C[Mg]Br.Br[C:48]1[CH:49]=[C:50]([CH:74]=[CH:75][CH:76]=1)/[CH:51]=[C:52]1\[CH2:53][CH2:54][C:55]2[N:56]([S:64]([C:67]3[CH:73]=[CH:72][C:70]([CH3:71])=[CH:69][CH:68]=3)(=[O:66])=[O:65])[C:57]([C:60]([O:62][CH3:63])=[O:61])=[CH:58][C:59]\1=2.C1(B(O)O)C=CC=CC=1>>[C:51]1([C:50]2[CH:49]=[CH:48][CH:76]=[CH:75][CH:74]=2)[CH:60]=[CH:57][CH:58]=[C:59]([CH2:55][CH:25]2[C:32]3[CH:31]=[C:30]([C:33]([O:35][CH3:36])=[O:34])[NH:29][C:28]=3[CH2:27][CH2:26]2)[CH:52]=1.[C:48]1([C:13]2[CH:19]=[CH:18][CH:16]=[CH:15][CH:14]=2)[CH:76]=[CH:75][CH:74]=[C:50](/[CH:51]=[C:52]2\[CH2:53][CH2:54][C:55]3[N:56]([S:64]([C:67]4[CH:73]=[CH:72][C:70]([CH3:71])=[CH:69][CH:68]=4)(=[O:65])=[O:66])[C:57]([C:60]([O:62][CH3:63])=[O:61])=[CH:58][C:59]\2=3)[CH:49]=1

Participants

6

Reactant 4

HCID 66827Phenylboronic AcidHCID 66873689(E)-methyl 4-(3-bromobenzylidene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 86638796Methyl 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)HCID 178419662HCID 178419662, compound

Product 2

HCID 59180092Methyl 4-(biphenyl-3-ylmethyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 67269515(E)-methyl 4-(biphenyl-3-ylmethylene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Procedure

The title compound was synthesized in four steps. First 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) (1.50 g, 8.37 mmol) was reacted with 3-bromobenzylmagnesium bromide (15 mL, 3.75 mmol) according to General Procedure 3 to give exo olefin-containing compound (E)-methyl 4-(3-bromobenzylidene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate, followed by coupling with phenylboronic acid (0.305 g, 2.50 mmol) according to General Procedure 9.2 to give (E)-methyl 4-(biphenyl-3-ylmethylene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate, then tosyl deprotection according to General Procedure 10.1 to give (E)-methyl 4-(biphenyl-3-ylmethylene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate. Hydrogenation of (E)-methyl 4-(biphenyl-3-ylmethylene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate according to General Procedure 6 (with 5% Pd/C), then purification by column chromatography (Isco CombiFlash) eluting with a gradient of 0-20% EtOAc/heptane afforded the title compound: 0.041 g. 1H NMR (400 MHz, ACETONE-d6) δ ppm 2.09-2.19 (m, 1H) 2.50-2.60 (m, 1H) 2.60-2.68 (m, 2H) 2.86 (d, J=1.85 Hz, 1H) 2.88 (s, 1H) 3.31-3.39 (m, 1H) 3.71-3.72 (m, 3H) 6.36 (d, J=1.90 Hz, 1H) 7.21-7.25 (m, 1H) 7.26-7.30 (m, 1H) 7.31-7.51 (m, 5H) 7.61-7.67 (m, 2H) 10.49 (br.s, 1H).

Workup

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Sources & evidence

ORD record
ord-d6668d032abd49ac8cd79c76d6f2625b
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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