Sodium Hydroxide → 6-fluoro-4-iodo-1H-benzo[d]imidazole

HRID 1013593Notes

Reaction equation

HRID 1013593 reaction equation
C(OC([N:8]1[C:12]2[CH:13]=[C:14]([F:18])[CH:15]=[C:16]([I:17])[C:11]=2[N:10]=[CH:9]1)=O)(C)(C)C.FC1C=C(N)C(N)=C(I)C=1.[OH-].[Na+]>C(O)=O>[F:18][C:14]1[CH:15]=[C:16]([I:17])[C:11]2[N:10]=[CH:9][NH:8][C:12]=2[CH:13]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 220590235-Fluoro-3-iodobenzene-1,2-diamine2×HCID 590217781H-Benzimidazole-1-carboxylic acid, 6-fluoro-4-iodo-, 1,1-dimethylethyl ester

Product 1

HCID 666515876-fluoro-4-iodo-1H-benzo[d]imidazoleYield 86%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

The 6-fluoro-4-iodo-benzoimidazole-1-carboxylic acid tert-butyl ester used in this step was prepared from 5-fluoro-3-iodo-benzene-1,2-diamine according to the procedure of Weber et al., WO 9400124. Briefly, a mixture of 5-fluoro-3-iodo-benzene-1,2-diamine (1.3 grams, 5.16 mmoles) and 1.5 mL of 96% formic acid was stirred at 100° for 3 hours, then cooled, and 35 mL 5% sodium hydroxide was added. The mixture was cooled in an ice bath and the resulting solid was collected, washed with water and dried in vacuo to provide 1.16 grams (86%) 6-fluoro-4-iodo-1H-benzoimidazole, m.p. 210-211° C. A mixture of 1.0 gram (3.8 mmoles) of this benzimidazole, di-tert-butyl dicarbonate (0.92 grams, 4.2 mmole), and 5 mg dimethylaminopyridine in 15 mL dioxane was stirred at 80° C. for 20 hours, then concentrated under reduced pressure. Purification of the residue by column chromatography over silica gel 230-400 mesh eluting with 30% ethyl acetate in hexane gave 6-fluoro-4-iodo-benzoimidazole-1-carboxylic acid tert-butyl ester as a crystalline solid, 1.38 grams (100%), m.p. 73-74° C.

Workup

  1. temperaturecooled
  2. temperatureThe mixture was cooled in an ice bath
  3. customthe resulting solid was collected
  4. washwashed with water
  5. customdried in vacuo

Sources & evidence

ORD record
ord-cdcd28221a774811a23fd5e75f027fe0
Source dataset
uspto-grants-2011_07
Patent number
US07981923B2

Reaction notes

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