Trifluoroacetic acid → 2,3-Dibromo-1-(3,4-difluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester

HRID 642543Notes

Reaction equation

HRID 642543 reaction equation
C(O[C:4]([C:6]1[C:10]([Br:11])=[C:9]([Br:12])[N:8]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:7]=1[CH2:21][N:22](C(OC(C)(C)C)=O)[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[O:5])C.CCC([O-])(C)C.[K+].[Cl-].[NH4+].C(O)(C(F)(F)[F:48])=O>C1(C)C=CC=CC=1>[CH2:27]([O:26][C:24]([C:23]1[C:4]([OH:5])=[C:6]2[C:10]([Br:11])=[C:9]([Br:12])[N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:48])[CH:15]=3)[C:7]2=[CH:21][N:22]=1)=[O:25])[CH3:28]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 23683543Potassium t-amylateHCID 684262634,5-dibromo-2-[(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-1-(4-fluoro-benzyl)-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 684283172,3-Dibromo-1-(3,4-difluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

To an ice/water bath cooled crude 4,5-dibromo-2-[(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-1-(4-fluoro-benzyl)-1H-pyrrole-3-carboxylic acid ethyl ester (29.49 g) in toluene (100 mL) was added a 25% (weight) concentration of potassium tert-pentoxide in toluene (67.04 mL) during a course of ˜5 min; after that, the reaction was stirred for 1 h in the cold bath and then poured to a stirring mixture of ice/water and ammonium chloride, organic phase was separated and washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated to give the cyclized intermediate. The intermediate was then dissolved in 50 mL toluene and 50 mL TFA and stirred at room temperature for 1 h, then concentrated, the residue was partitioned between toluene and water; the organic phase was washed once with saturated sodium hydrogen carbonate, saturated sodium chloride solution respectively, then dried over anhydrous sodium sulfate, filtered, and air bubbled through the filtrate for a period of overnight. The precipitates were collected as the first crop of the title product (8.161 g). The filtrate was concentrated and purified with column directly to give the second crop of the title product (4.98 g). The title compound, ESI MS (m/z): 489 (M+H)+.

Workup

  1. customwas separated
  2. washwashed with water and saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the cyclized intermediate
  7. concentrationconcentrated
  8. customthe residue was partitioned between toluene and water
  9. washthe organic phase was washed once with saturated sodium hydrogen carbonate, saturated sodium chloride solution respectively
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customair bubbled through the filtrate for a period of overnight
  13. customThe precipitates were collected as the first crop of the title product (8.161 g)
  14. concentrationThe filtrate was concentrated
  15. custompurified with column directly

Sources & evidence

ORD record
ord-6ae2aae8fe45453ca8c1ca5361e5a275
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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