Sodium Hydroxide → HCID 59853575, compound

HRID 2374398Notes

Reaction equation

HRID 2374398 reaction equation
[CH2:1]([O:4][C:5]([C:7]1[NH:8][CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])[CH:2]=[CH2:3].[Cl-].[NH4+:14].[OH-].[Na+].[OH-].[NH4+]>[Cl-].C([N+](CCCCCCCC)(CCCCCCCC)C)CCCCCCC.C(OC)(C)(C)C>[CH2:1]([O:4][C:5]([C:7]1[N:8]([NH2:14])[CH:9]=[C:10]([F:12])[CH:11]=1)=[O:6])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 59853565HCID 59853565, compound

Product 1

HCID 59853575HCID 59853575, compoundYield 74.6%

Reagents, catalysts & solvents 2

HCID 21218Trioctylmethylammonium chlorideCatalystHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
25 °C

Procedure

1-Amino-4-fluoro-1H-pyrrole-2-carboxylic acid allyl ester was prepared following the N-amination procedure described in Tetrahedron Lett., 47, 5341-43 (2006). 4-Fluoro-1H-pyrrole-2-carboxylic acid allyl ester (Example 14e, 2.49 g, 14.74 mmol) was mixed together with solid ammonium chloride (4.81 g, 90.75 mmol), 30% aqueous sodium hydroxide solution (42.4 mL), 29.56% aqueous ammonium hydroxide solution (13.71 mL) and trioctylmethylammonium chloride (“Aliquat® 336”, 0.166 g, 0.411 mmol) in methyl tert-butyl ether (50 mL). Under vigorous stirring, a 6.15% aqueous bleach solution (“Chlorox”, 146 mL) was slowly added via addition funnel upon which the color of the solution turned orange. After stirring for 2 h at 25° C., the layers were separated and the aqueous layer was extracted with methyl tert-butyl ether (2×10 mL). The combined organic layers were washed with a saturated sodium thiosulfate solution (50 mL) and the organic layer was dried over sodium sulfate and filtered. The solvent was removed in vacuo and the crude product was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 20% ethyl acetate in hexanes) to afford the desired product, 1-amino-4-fluoro-1H-pyrrole-2-carboxylic acid allyl ester (2.02 g, 10.99 mmol, 62.1% yield). 1H NMR (400 MHz, CDCl3) δ: 4.73 (2H, d, J=5.5 Hz), 5.26-5.29 (1H, m), 5.34-5.40 (1H, m), 5.52 (2H, bs), 5.93-6.02 (1H, m), 6.49-6.53 (1H, m), 6.78-6.80 (1H, m).

Workup

  1. custom1-Amino-4-fluoro-1H-pyrrole-2-carboxylic acid allyl ester was prepared
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with methyl tert-butyl ether (2×10 mL)
  4. washThe combined organic layers were washed with a saturated sodium thiosulfate solution (50 mL)
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed in vacuo
  8. customthe crude product was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-14117237bc4740499642acefa52ef365
Source dataset
uspto-grants-2008_12
Patent number
US07462611B2

Reaction notes

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