4-(Trifluoromethyl)phenylboronic acid → Methyl 4-((4'-(trifluoromethyl)biphenyl-3-yl)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601831Notes

Reaction equation

HRID 601831 reaction equation
CC1C2C(=O)CCC=2N(S(C2C=CC(C)=CC=2)(=O)=O)C=1C(O)=O.O=C1C2C=C(C(OC)=O)NC=2CC1.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.[F:77][C:78]([F:89])([F:88])[C:79]1[CH:84]=[CH:83][C:82](B(O)O)=[CH:81][CH:80]=1>>[F:77][C:78]([F:89])([F:88])[C:79]1[CH:84]=[CH:83][C:82]([C:48]2[CH:76]=[CH:75][CH:74]=[C:50]([CH2:51][CH:52]3[C:59]4[CH:58]=[C:57]([C:60]([O:62][CH3:63])=[O:61])[NH:56][C:55]=4[CH2:54][CH2:53]3)[CH:49]=2)=[CH:81][CH:80]=1.[S:64]([N:56]1[C:57]([C:60]([O:62][CH3:63])=[O:61])=[CH:58][C:59]2/[C:52](=[CH:51]/[C:50]3[CH:49]=[C:48]([C:82]4[CH:83]=[CH:84][C:79]([C:78]([F:89])([F:88])[F:77])=[CH:80][CH:81]=4)[CH:76]=[CH:75][CH:74]=3)/[CH2:53][CH2:54][C:55]1=2)([C:67]1[CH:68]=[CH:69][C:70]([CH3:71])=[CH:72][CH:73]=1)(=[O:65])=[O:66]

Participants

6

Reactant 4

HCID 27343894-(Trifluoromethyl)phenylboronic 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 59180217Methyl 4-((4'-(trifluoromethyl)biphenyl-3-yl)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 66874589(E)-methyl 1-tosyl-4-((4'-(trifluoromethyl)biphenyl-3-yl)methylene)-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 4-(trifluoromethyl)phenylboronic acid (0.178 g, 0.94 mmol) according to General Procedure 9.1 to give (E)-methyl 1-tosyl-4-((4′-(trifluoromethyl)biphenyl-3-yl)methylene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate, then tosyl deprotection according to General Procedure 10.1 to give (E)-methyl 4-((4′-(trifluoromethyl)biphenyl-3-yl)methylene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate. Hydrogenation of (E)-methyl 4-((4′-(trifluoromethyl)biphenyl-3-yl)methylene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate according to General Procedure 6 (with 5% Pd/C), then purification provided the title compound, which was used without purification in the next step. 0.047 g. 19F NMR (376 MHz, ACETONE-d6) δ ppm −63.27 (s, 3F); LCMS-MS (ESI−) 398.0 (M−H).

Workup

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Sources & evidence

ORD record
ord-a9efce19e0a344aaa61a2f81c3603243
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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