Water → HCID 69022513, compound

HRID 1865068Notes

Reaction equation

HRID 1865068 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][CH:8]=[C:9]([C:25]#[N:26])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][CH:12]=1)=[O:5])[CH3:2].[C:27]([O-])([O-])=O.[K+].[K+].IC.O>CS(C)=O.CCOC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:27])[CH:8]=[C:9]([C:25]#[N:26])[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][CH:12]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 11430Potassium Carbonate2×HCID 69021064ethyl 3-(4-(benzyloxy)phenyl)-4-cyano-1H-pyrrole-2-carboxylate

Product 1

HCID 69022513HCID 69022513, compoundYield 66.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-(4-benzyloxy-phenyl)-4-cyano-1H-pyrrole-2-carboxylic acid ethyl ester (266.70 g, 0.770 mol) in DMSO (2,000 mL) is treated with K2CO3 (117.06 g, 0.847 mol). The resulting solution is allowed to stir at room temperature for several minutes, then treated with iodomethane (58.00 mL, 0.931 mol). The resulting reaction mixture is allowed to stir at room temperature overnight. An additional 0.5 eq of iodomethane (24.00 mL, 0.385 mol) and 0.6 eq of K2CO3 (63.85 g, 0.462 mol) are added to the reaction. The reaction mixture is allowed to stir at room temperature for 2 hours. The reaction mixture is divided into 2 equal portions and each portion is poured into water (2,000 mL) and extracted with EtOAc (3×700 mL each). The combined organics are washed with H2O (2×1000 mL each), dried over anhydrous MgSO4, filtered, then concentrated in vacuo to afford a residue. The residue is slurried in EtOAc (300 mL), then treated with excess hexanes, causing a solid to precipitate. The solid is recovered by vacuum filtration, washing with hexanes, and drying under vacuum filtration to afford the title compound, 3-(4-benzyloxy-phenyl)-4-cyano-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester, (184.73 g, 66% yield) as a light-brown solid: 1H NMR (500 MHz; CDCl3) δ 7.46 (d, 2H), 7.39 (m, 2H), 7.32 (m, 3H), 7.24 (s, 1H), 7.00 (d, 2H), 5.10 (s, 2H), 4.13 (q, 2H), 3.95 (s, 3H), 1.06 (t, 3H); MS(ES): m/z 361.1 (M++H).

Workup

  1. customThe resulting reaction mixture
  2. stirringto stir at room temperature overnight
  3. stirringto stir at room temperature for 2 hours
  4. extractionextracted with EtOAc (3×700 mL each)
  5. washThe combined organics are washed with H2O (2×1000 mL each)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a residue
  10. customto precipitate
  11. filtrationThe solid is recovered by vacuum filtration
  12. washwashing with hexanes
  13. customdrying under vacuum filtration

Sources & evidence

ORD record
ord-78f48f77000d41c1addb5b3248bf2f25
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Reaction notes

Loading…