Citric Acid → 4-chloro-5-[(methyloxy)carbonyl]-1H-pyrrole-3-carboxylic acid

HRID 1875004Notes

Reaction equation

HRID 1875004 reaction equation
[Cl:1][C:2]1[C:6]([CH:7]=[O:8])=[CH:5][NH:4][C:3]=1[C:9]([O:11][CH3:12])=[O:10].CC(=CC)C.C1C[O:21]CC1.P([O-])(O)(O)=O.[Na+].Cl([O-])=O.[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)(C)(C)C.O.CCOC(C)=O>[Cl:1][C:2]1[C:6]([C:7]([OH:21])=[O:8])=[CH:5][NH:4][C:3]=1[C:9]([O:11][CH3:12])=[O:10]

Participants

10

Reactant 6

HCID 311Citric AcidHCID 8028TetrahydrofuranHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86644899Methyl 3-chloro-4-formyl-1H-pyrrole-2-carboxylate

Product 1

HCID 684862114-chloro-5-[(methyloxy)carbonyl]-1H-pyrrole-3-carboxylic acidYield 92%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 3-chloro-4-formyl-1H-pyrrole-2-carboxylate (0.5 g, 2.67 mmol) dissolved in tert-butanol (25 mL) was added 2-methyl-2-butene/2M in THF (20.26 mL, 40.5 mmol). A solution of sodium dihydrogen phosphate monoH2O (2.57 g, 18.66 mmol) and sodium chlorite (2.170 g, 23.99 mmol) in water (25.00 mL) was added dropwise over a period of 15 min. The solution was stirred at RT for 2.5 h. Aqueous citric acid (10 w/w %) was added until a pH of 4-5 was observed. EtOAc (50 mL) was added, the layers separated and the aqueous layer extracted with EtOAc (2×25 mL). The organic layers were combined, dried over sodium sulfate filtered and evaporated. The crude material was triturated with a minimal amount of EtOAc to afford 4-chloro-5-[(methyloxy)carbonyl]-1H-pyrrole-3-carboxylic acid (0.5 g, 92% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 14.4 (br. s., 1H), 12.4 (br. s., 1H) 7.51 (d, 1H) 3.78 (s, 3H). MS: m/z 202.0 (M−1).

Workup

  1. customthe layers separated
  2. extractionthe aqueous layer extracted with EtOAc (2×25 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude material was triturated with a minimal amount of EtOAc

Sources & evidence

ORD record
ord-1ed6f71f371a43e8be3386b3e745051c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…