Tosylmethyl isocyanide → ethyl 4-(4-nitrophenyl)-1H-pyrrole-3-carboxylate

HRID 2197514Notes

Reaction equation

HRID 2197514 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[N+:11]([CH2:13]S(C1C=CC(C)=CC=1)(=O)=O)#[C-:12].[N+:24]([C:27]1[CH:32]=[CH:31][C:30](/[CH:33]=[CH:34]/[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:29][CH:28]=1)([O-:26])=[O:25].C(=O)(O)[O-].[Na+]>C1COCC1>[N+:24]([C:27]1[CH:28]=[CH:29][C:30]([C:33]2[C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:12][NH:11][CH:13]=2)=[CH:31][CH:32]=1)([O-:26])=[O:25]

Participants

6

Reactant 4

HCID 161915Tosylmethyl isocyanideHCID 516892Sodium BicarbonateHCID 1268038Ethyl 4-nitrocinnamateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 53440113ethyl 4-(4-nitrophenyl)-1H-pyrrole-3-carboxylateYield 62.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cooled (−77° C.) solution of 1M lithium hexamethyldisilazide in THF (102.4 mL, 102.4 mmol) was added 1-[(isocyanomethyl)sulfonyl]-4-methylbenzene (20.0 g, 102.4 mmol) as a solution in THF (100 mL) dropwise (30 min). The solution was allowed to stir for 15 min, and then ethyl (2E)-3-(4-nitrophenyl)acrylate (22.66 g, 102.4 mmol) was added dropwise (1 h) as a solution in THF (250 mL). The reaction was allowed to warm to rt over 17 h and the aqueous saturated sodium bicarbonate solution (200 mL) was added. The product was extracted with ethyl acetate (3×300 mL), and then the combined organic extracts were washed with water (100 mL), dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using 0-5% ethylacetate/dichlromethane to afford the desired product (16.65 g, 62%). 1H-NMR (300 MHz, DMSO-d6) δ 11.78 (br s, 1H), 8.15-8.19 (m, 2H), 7.73-7.76 (m, 2H), 7.55-7.79 (m, 1H), 7.19-7.24 (m, 1H), 4.16 (q, J=7.1 Hz, 2H), 1.21 (t, J=7.1 Hz, 3H); HPLC (Method A) 2.90 min; TLC Rf=0.47 (95:5 v/v CH2Cl2-EtOAc).

Workup

  1. extractionThe product was extracted with ethyl acetate (3×300 mL)
  2. washthe combined organic extracts were washed with water (100 mL)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3dd39cf8fcc74b63bd9efb3aa37b0b9b
Source dataset
uspto-grants-2012_12
Patent number
US08338594B2

Reaction notes

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