Sodium Bicarbonate → 5-(Benzoxazol-2-yl)-2-hydroxymethyl-1-(tetrahydropyran-4-yl)benzimidazole

HRID 74171Notes

Reaction equation

HRID 74171 reaction equation
C([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:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[OH:30])=O)=[CH:20][C:8]=2[N:7]=1)(=O)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+].O1C2C=CC(C3C=CC4N(C5CCOCC5)C(COC(=O)C)=NC=4C=3)=CC=2N=C1>C1(C)C=CC=CC=1>[O:30]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]=[C:21]1[C:19]1[CH:18]=[CH:17][C:9]2[N:10]([CH:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)[C:6]([CH2:5][OH:4])=[N:7][C:8]=2[CH:20]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 674982825-(Benzoxazol-5-yl)-2-acetoxymethyl-1-(tetrahydropyran-4-yl)benzimidazoleHCID 674988482-Acetoxymethyl-5-(2-hydroxyanilinocarbonyl)-1-(tetrahydropyran-4-yl)benzimidazole

Product 1

HCID 674979855-(Benzoxazol-2-yl)-2-hydroxymethyl-1-(tetrahydropyran-4-yl)benzimidazole

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

An eggplant flask (50 mL) was charged with 2-acetoxymethyl-5-(2-hydroxyanilinocarbonyl)-1-(tetrahydropyran-4-yl)benzimidazole (see Working Example 13-1) (0.50 g, 1.22 mmol) toluene (6.3 mL), and p-toluenesulfonic acid hydrate (1.60 g, 8.41 mmol), and this was refluxed for 1.5 hours. After being allowed to cool, the liquid was made neutral with saturated aqueous sodium hydrogen carbonate. The precipitated crystals were filtered off and washed successively with toluene and hexane, then dried under reduced pressure with heating to yield a mixture of the title compound and 5-(benzoxazol-5-yl)-2-acetoxymethyl-1-(tetrahydropyran-4-yl)benzimidazole (0.25 g: estimated to contain 0.57 mmol and 0.13 mmol, respectively, according to 1H-NMR) as a white powder. This mixture and methanol (7 mL) were charged to an eggplant flask (50 mL) to which was then added an aqueous solution of lithium hydroxide (1 M, 0.3 mL), and after stirring for 30 m the liquid was made pH 6 with dilute hydrochloric acid (1 M). The precipitated crystals were filtered off, washed with distilled water, and dried under reduced pressure with heating to yield the title compound (0.07 g, 16.4% yield) as a light pinkish-white powder.

Workup

  1. temperaturethis was refluxed for 1.5 hours
  2. temperatureto cool
  3. filtrationThe precipitated crystals were filtered off
  4. washwashed successively with toluene and hexane
  5. customdried under reduced pressure
  6. temperaturewith heating
  7. customto yield

Sources & evidence

ORD record
ord-a00e80a9741246919eed2a30326d47a4
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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