N-bromobutanimide → HCID 178497004, compound

HRID 31965Notes

Reaction equation

HRID 31965 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4].C1COCC1.CO.C1C(=O)N([Br:37])C(=O)C1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CO>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:37])=[CH:17][C:16]=2[CH3:21])=[C:12]([F:22])[C:8]2[NH:9][CH:10]=[N:11][C:7]=2[CH:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 67184N-bromobutanimide2×HCID 521998p-Toluenesulfonic acid monohydrateHCID 21899815MeOH tetrahydrofuran2×HCID 178497005HCID 178497005, compound

Product 1

HCID 178497004HCID 178497004, compoundYield 79.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

7-Fluoro-6-o-tolylamino-1H-benzoimidazole-5-carboxylic acid methyl ester 7a (2.00 g, 6.68 mmol) is suspended in 1:1 THF/MeOH (60 mL) and cooled to −78° C. under a nitrogen atmosphere. A solution of NBS (1.20 g, 6.75 mmol) in 1:1 THF/MeOH (5 mL) is added followed by a MeOH (5 mL) solution of TsOH.H2O (1.9 g, 10.0 mmol). After 30 minutes, the reaction mixture is warmed to 0° C. and then after 1 hour warmed to room temperature. After 16 hours, more NBS (0.12 g, 0.67 mmol) is added and the reaction mixture is allowed to stir for 3 hours. The reaction mixture is quenched by the addition of 10% Na2S2O4 solution. After 30 minutes, the reaction mixture is diluted with water and ethyl acetate and the layers separated. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. The recovered solid is triturated with methylene chloride to give 2.00 g (79%) pure desired product: MS APCI (+) m/z 380, 378 (M+1 Br pattern) detected.

Workup

  1. temperaturethe reaction mixture is warmed to 0° C.
  2. temperatureafter 1 hour warmed to room temperature
  3. waitAfter 16 hours
  4. customThe reaction mixture is quenched by the addition of 10% Na2S2O4 solution
  5. waitAfter 30 minutes
  6. additionthe reaction mixture is diluted with water and ethyl acetate
  7. customthe layers separated
  8. extractionThe aqueous layer is extracted with ethyl acetate
  9. dry with materialThe combined organic extracts are dried (Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe recovered solid is triturated with methylene chloride

Sources & evidence

ORD record
ord-0769676493a7466a86f677e46f2d8488
Source dataset
uspto-grants-2008_09
Patent number
US07425637B2

Reaction notes

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