4-(Hydroxymethyl)benzeneboronic acid → Methyl 4-((4'-(hydroxymethyl)biphenyl-3-yl)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601833Notes

Reaction equation

HRID 601833 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)/[CH:5]=[C:6]1\[CH2:7][CH2:8][C:9]2[N:10]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:13]\1=2.[OH:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1>>[OH:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:2]2[CH:30]=[CH:29][CH:28]=[C:4]([CH2:5][CH:6]3[C:13]4[CH:12]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[NH:10][C:9]=4[CH2:8][CH2:7]3)[CH:3]=2)=[CH:35][CH:34]=1.[OH:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:29]2[CH:30]=[CH:2][CH:3]=[C:4](/[CH:5]=[C:6]3\[CH2:7][CH2:8][C:9]4[N:10]([S:18]([C:21]5[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=5)(=[O:19])=[O:20])[C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:13]\3=4)[CH:28]=2)=[CH:35][CH:34]=1

Participants

4

Reactant 2

HCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 66873689(E)-methyl 4-(3-bromobenzylidene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Product 2

HCID 59180154Methyl 4-((4'-(hydroxymethyl)biphenyl-3-yl)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateHCID 66873868(E)-methyl 4-((4'-(hydroxymethyl)biphenyl-3-yl)methylene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Procedure

The title compound was synthesized in three steps. First, (E)-methyl 4-(3-bromobenzylidene)-1-tosyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.301 g, 0.62 mmol) was coupled with 4-(hydroxymethyl)phenylboronic acid (0.141 g, 0.93 mmol) according to General Procedure 9.1 to give (E)-methyl 4-((4′-(hydroxymethyl)biphenyl-3-yl)methylene)-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-((4′-(hydroxymethyl)biphenyl-3-yl)methylene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate. Hydrogenation of (E)-methyl 4-((4′-(hydroxymethyl)biphenyl-3-yl)methylene)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate according to General Procedure 6 (with 5% Pd/C), provided the title compound, which was used without purification in the next step. 1H NMR (400 MHz, ACETONE-d6) δ ppm 2.10-2.20 (m, 1H), 2.51-2.60 (m, 1H), 2.61-2.68 (m, 2H), 2.87 (dd, J=7.25, 2.03 Hz, 2H), 3.35 (quin, J=6.88 Hz, 1H), 3.71 (s, 3H), 4.20 (br. s, 1H), 4.67 (s, 2H), 6.35-6.37 (m, 1H), 7.23 (d, J=7.76 Hz, 1H), 7.35-7.40 (m, 1H), 7.42-7.46 (m, 2H), 7.47-7.51 (m, 2H) 7.59-7.63 (m, 2H), 10.48 (br. s, 1H); LCMS-MS (ESI+) 384.0 (M+Na).

Sources & evidence

ORD record
ord-6fc1f24874e5415a8398144ab127f099
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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