Hydrochloric Acid → Ethyl 3-(4-bromophenyl)-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylate

HRID 1865107Notes

Reaction equation

HRID 1865107 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:16])[C:8]([CH2:14][CH3:15])=[C:9]([C:12]#[N:13])[C:10]=1I)=[O:5])[CH3:2].[Br:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu].C(O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:16])[C:8]([CH2:14][CH3:15])=[C:9]([C:12]#[N:13])[C:10]=1[C:21]1[CH:22]=[CH:23][C:18]([Br:17])=[CH:19][CH:20]=1)=[O:5])[CH3:2]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 79599(4-Bromophenyl)boronic acidHCID 516892Sodium BicarbonateHCID 57975348HCID 57975348, compound

Product 1

HCID 16037629Ethyl 3-(4-bromophenyl)-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylateYield 78.2%

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A 10 mL round bottom flask is charged with 4-cyano-5-ethyl-3-iodo-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (200 mg, 0.602 mmol, prepared in preparation 38) and absolute ethanol (4.0 mL). To this solution is added 4-bromophenylboronic acid (242 mg, 1.20 mmol) and 2M aqueous Na2CO3 solution (0.90 mL). This mixture is degassed under house vacuum for about 20 min until no bubbles produced. Nitrogen gas is recharged into the flask and Pd(PPh3)4 (56 mg, 0.048 mmol) is quickly added. The septum cap is well sealed with copper wire and teflon tape. The mixture in this sealed flask is then heated in oil bath at 80° C. for 18-20 hours. The mixture is cooled to room temperature. It is diluted in methylene chloride (20 mL) and poured into 0.1 M HCl solution (30 mL), pH is adjusted to 7-8 with sat. aq. NaHCO3 solution. The mixture is extracted with methylene chloride (2×30 mL), and diethyl ether (2×30 mL), the combined extracts are dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue is then purified by flash chromatography (silica gel, elution with 20% Et2O in hexanes) to provide the title compound (170 mg, 77%) as a light brown oil. Mass spectrum (m/e): 360.9 (M+1). Rf=0.4 (50% of Et2O in hexanes).

Workup

  1. customThis mixture is degassed under house vacuum for about 20 min until no bubbles
  2. customproduced
  3. additionis quickly added
  4. customThe septum cap
  5. temperatureThe mixture is cooled to room temperature
  6. extractionThe mixture is extracted with methylene chloride (2×30 mL), and diethyl ether (2×30 mL)
  7. dry with materialthe combined extracts are dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is then purified by flash chromatography (silica gel, elution with 20% Et2O in hexanes)

Sources & evidence

ORD record
ord-1256069235d041939872f64abdeb66f3
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

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