Acetic Acid → HCID 71598746, compound

HRID 1507723Notes

Reaction equation

HRID 1507723 reaction equation
[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12](I)[N:11]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:10]=1[C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=1)CCC.CC(O)=O>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=2)[N:11]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:10]=1[C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 6077842-(Tributylstannyl)pyridineHCID 89610330HCID 89610330, compound

Product 1

HCID 71598746HCID 71598746, compoundYield 84.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of ethyl 3,4-bis(benzyloxy)-5-iodo-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (28) (300 mg, 0.51 mmol) in DMF (5 mL) was added 2-(tributylstannyl)pyridine (280 μL, 0.87 mmol), copper(I) iodide (19.6 mg, 0.10 mmol) and dichlorobis(triphenylphosphine)palladium(II) (36.1 mg, 0.05 mmol). The mixture was heated in a microwave at 140° C. for 30 min, AcOH (2 mL) was added and the crude product was loaded onto a column of SCX (5 g). The column was washed with MeOH and then the product was eluted with 1% NH3 in MeOH. The resultant mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (12 g, 20-100% EtOAc in isohexane) to afford ethyl 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-5-(pyridin-2-yl)-1H-pyrrole-2-carboxylate (UL1-082) (231 mg, 83%) as a pale yellow oil: m/z 535 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 1H NMR (400 MHz, DMSO-d6) δ: 8.47-8.40 (m, 1H), 7.71-7.63 (m, 1H), 7.54-7.47 (m, 2H), 7.45-7.16 (m, 10H), 7.12-7.03 (m, 2H), 6.83-6.76 (m, 2H), 5.18 (s, 2H), 4.96 (s, 2H), 4.02 (q, J=7.1 Hz, 2H), 3.72 (s, 3H), 1.03 (t, J=7.1 Hz, 3H).

Workup

  1. washThe column was washed with MeOH
  2. washthe product was eluted with 1% NH3 in MeOH
  3. concentrationThe resultant mixture was concentrated in vacuo
  4. customthe residue was purified by silica gel chromatography (12 g, 20-100% EtOAc in isohexane)

Sources & evidence

ORD record
ord-649555d5b9394c568bb67d3e55044935
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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