2-Aminophenol → 2-Acetoxymethyl-5-(2-hydroxyanilinocarbonyl)-1-(tetrahydropyran-4-yl)benzimidazole

HRID 74170Notes

Reaction equation

HRID 74170 reaction equation
[C:1]([O:4][CH2:5][C:6]1[N:10]([CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:9]2[CH:17]=[CH:18][C:19]([C:21]([OH:23])=O)=[CH:20][C:8]=2[N:7]=1)(=[O:3])[CH3:2].C(Cl)(=O)C(Cl)=O.C(NC(C)C)(C)C.[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[OH:44]>O1CCCC1.CN(C)C=O>[C:1]([O:4][CH2:5][C:6]1[N:10]([CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[C:9]2[CH:17]=[CH:18][C:19]([C:21]([NH:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[OH:44])=[O:23])=[CH:20][C:8]=2[N:7]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 58012-AminophenolHCID 7912DiisopropylamineHCID 65578Oxalyl chlorideHCID 674979142-Acetoxymethyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid

Product 1

HCID 674988482-Acetoxymethyl-5-(2-hydroxyanilinocarbonyl)-1-(tetrahydropyran-4-yl)benzimidazoleYield 124.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

A 4-neck flask (200 mL) equipped with a reflux condenser was charged with 2-acetoxymethyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid (see Working Example 7-1) (1.50 g, 4.71 mmol), anhydrous tetrahydrofuran (40 mL), and oxalyl chloride (0.657 g, 5.18 mmol), and anhydrous N,N-dimethylformamide (0.4 mL) was then added dropwise at room temperature, after which the reaction mixture was stirred at 50° C. for 14 hours. After being allowed to cool to room temperature, the solvent was distilled off under reduced pressure to give a pale yellow residue which was cooled to 0 to 5° C., which was taken up in anhydrous tetrahydrofuran (40 mL) and diisopropylamine (0.79 mL, 5.65 mmol), followed by 2-aminophenol (0.57 g, 5.81 mmol), and this was stirred for 24 hours at room temperature. The precipitated crystals were filtered off, these were washed with tetrahydrofuran and dried under reduced pressure with heating to yield the title compound (2.40 g, quant.) as a white powder.

Workup

  1. customA 4-neck flask (200 mL) equipped with a reflux condenser
  2. additionwas then added dropwise at room temperature
  3. temperatureto cool to room temperature
  4. distillationthe solvent was distilled off under reduced pressure
  5. customto give a pale yellow residue which
  6. temperaturewas cooled to 0 to 5° C.
  7. stirringthis was stirred for 24 hours at room temperature
  8. filtrationThe precipitated crystals were filtered off
  9. washthese were washed with tetrahydrofuran
  10. customdried under reduced pressure
  11. temperaturewith heating

Sources & evidence

ORD record
ord-5f82801a64e24b30ab64b9cd444da363
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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