Sodium hydride → Methyl 4-(trifluoromethyl)-1H-pyrrole-3-carboxylate

HRID 43007Notes

Reaction equation

HRID 43007 reaction equation
[H-].[Na+].C1(C)C=CC(S([CH2:12][N+:13]#[C-:14])(=O)=O)=CC=1.[F:16][C:17]([F:25])([F:24])/[CH:18]=[CH:19]/[C:20]([O:22][CH3:23])=[O:21].CCOCC.CS(C)=O>CCOCC.CCOC(C)=O>[F:16][C:17]([F:25])([F:24])[C:18]1[C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:12][NH:13][CH:14]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 5371282Methyl 4,4,4-trifluorocrotonateHCID 19869614Ether dimethylsulfoxide

Product 1

HCID 57699539Methyl 4-(trifluoromethyl)-1H-pyrrole-3-carboxylateYield 24.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a round-bottomed flask was added sodium hydride (3.24 mmol, 78 mg) in Et2O (5 mL). A mixture of p-toluenesulfonylmethyl isocyanide (3.24 mmol, 634 mg) and (E)-methyl 4,4,4-trifluorobut-2-enoate (3.24 mmol, 500 mg) were added in a 2:1 mixture of Et2O/DMSO (22.5 mL). The reaction mixture was stirred for a further 30 min then quenched with H2O (10 mL) and extracted with Et2O (×3). The Et2O layers were combined and washed with brine, dried over MgSO4, filtered and the solvent removed to give a yellow/orange solid. Purification by flash chromatography (1:4 EtOAc:Hept) the desired product (154 mg, 0.80 mmol, 24.6%). 1H NMR (400 MHz, CD3OD) δ 3.79 (s, 3H) 7.20 (s, 1H) 7.50 (s, 1H).

Workup

  1. customthen quenched with H2O (10 mL)
  2. extractionextracted with Et2O (×3)
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed
  7. customto give a yellow/orange solid

Sources & evidence

ORD record
ord-1e4722b3476d46b49f16232b6bf38de3
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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