1,2-Dichloroethane → HCID 59180070, compound

HRID 601819Notes

Reaction equation

HRID 601819 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][CH3:9])=[O:7].[Br:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18](O)=[O:19])=[CH:13][CH:12]=1.Cl[CH2:22][CH2:23]Cl>>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH:18]2[C:4]3[CH:3]=[C:2]([C:6]([O:8][CH3:9])=[O:7])[NH:1][C:5]=3[CH2:23][CH2:22]2)=[CH:13][CH:12]=1.[Br:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([C:4]2[CH:3]=[C:2]([C:6]([O:8][CH3:9])=[O:7])[NH:1][CH:5]=2)=[O:19])=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 74654Benzeneacetic acid, 4-bromo-HCID 136930Methyl pyrrole-2-carboxylate

Product 2

HCID 59180070HCID 59180070, compoundHCID 66874479HCID 66874479, compound

Procedure

The title compound was synthesized in six steps. First, methyl 1H-pyrrole-2-carboxylate (1.0 g, 8 mmol, 1 equiv) in DCE (15 mL) was reacted with 4-bromophenylacetic acid (2.06 g, 9.6 mmol, 1.2 equiv) according to General Procedure 1.2.A to afford methyl 4-(2-(4-bromophenyl)acetyl)-1H-pyrrole-2-carboxylate, which was then BOC-protected according to General Procedure 1.2.B to provide 1-tert-butyl 2-methyl 4-(2-(4-bromophenyl)acetyl)-1H-pyrrole-1,2-dicarboxylate, which was next reacted with 2-tert-butoxy-2-oxoethylzinc chloride (3.0 g, 28.2 mL, 0.5M in ether, 14 mmol, 3.5 equiv) according to General Procedure 1.2.C to afford 1-tert-butyl 2-methyl 4-(1-(4-bromophenyl)-4-tert-butoxy-2-hydroxy-4-oxobutan-2-yl)-1H-pyrrole-1,2-dicarboxylate, which was reacted with trifluoroacetic acid (8.25 mL, 0.45 M) and triethylsilane (1.25 g, 1.72 mL, 2.9 equiv) according to General Procedure 1.2.D to provide 4-(4-bromophenyl)-3-(5-(methoxycarbonyl)-1H-pyrrol-3-yl)butanoic acid. This product was then cyclized by reaction with PPA (3.16 g) according to General Procedure 1.2.E to achieve methyl 4-(4-bromobenzyl)-6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate. Reduction with decaborane (0.34 g, 3 mmol, 5 equiv) according to Procedure 5b afforded the title compound, which was purified by purified by column chromatography (Isco CombiFlash) using a 0-30% gradient (EtOAc/Heptane). 0.0998 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.03-2.16 (m, 1H) 2.58 (dt, J=12.39, 6.88 Hz, 1H) 2.66 (t, J=6.99 Hz, 2H) 2.76 (d, J=7.39 Hz, 2H) 3.28 (dq, J=7.18, 6.92 Hz, 1H) 3.81 (s, 3H) 6.38 (d, J=1.48 Hz, 1H) 7.07 (d, J=8.31 Hz, 2H) 7.42 (q, J=4.17 Hz, 2H) 8.82 (br. s, 1H).

Sources & evidence

ORD record
ord-94c4fb415eb24a5ab5f11f7e127f3fcb
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

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