Ethanol → (2'-(1H-Tetrazol-5-yl)biphenyl-4-yl)methanol

HRID 644928Notes

Reaction equation

HRID 644928 reaction equation
O1CCCCC1[N:7]1[N:11]=[N:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[CH:23]=[CH:22][C:21]([CH2:24][O:25]C3CCCCO3)=[CH:20][CH:19]=2)=[N:8]1.C(O)C.S(=O)(=O)(O)O.[OH-].[Na+]>O>[NH:10]1[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[CH:23]=[CH:22][C:21]([CH2:24][OH:25])=[CH:20][CH:19]=2)=[N:8][N:7]=[N:11]1

Participants

6

Reactant 4

HCID 702EthanolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 117505182-(tetrahydro-pyran-2-yl)-5-[4'-(tetrahydro-pyran-2-yloxymethyl)-biphenyl-2-yl]-2H-tetrazole

Product 1

HCID 178519405(2'-(1H-Tetrazol-5-yl)biphenyl-4-yl)methanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
45 °C

Procedure

To 2-(tetrahydro-pyran-2-yl)-5-[4′-(tetrahydro-pyran-2-yloxymethyl)-biphenyl-2-yl]-2H-tetrazole (3.36 g; 8.00 mmol) are added 94% ethanol (12 mL) and a 2 M aqueous solution of sulfuric acid (1.0 mL; 2.0 mmol). The resulting mixture is heated to 45° C. for 3.5 hours. Water (16 mL) is slowly added and the mixture is allowed to cool down to room temperature. The pH of the reaction mixture is adjusted to pH 2 to 3 by adding a 2M aqueous sodium hydroxide solution (0.6 mL). The mixture is concentrated under reduced pressure, diluted with isopropyl acetate (15 mL) and washed three times with water (3 mL). The organic extract is concentrated under reduced pressure to a volume of about 4 mL and tert-butyl methyl ether (8 mL in total) is slowly added. The mixture is stirred overnight, diluted with a small amount of isopropyl acetate and further stirred for 4.5 hours. The suspended, white solid is filtered, washed with a small amount of isopropyl acetate and dried under reduced pressure to afford [2′-(1H-tetrazol-5-yl)-biphenyl-4-yl]-methanol. The filtrate is concentrated under reduced pressure, and tert-butyl methyl ether (3 mL) and heptane (0.5 mL) are slowly added. The mixture is stirred at room temperature overnight and at 0 to 5° C. for 1 hour. The suspended, white solid is filtered, washed with a small amount of isopropyl acetate and dried under reduced pressure to afford a second crop of [2′-(1H-tetrazol-5-yl)-biphenyl4-yl]-methanol.

Workup

  1. temperatureto cool down to room temperature
  2. concentrationThe mixture is concentrated under reduced pressure
  3. additiondiluted with isopropyl acetate (15 mL)
  4. washwashed three times with water (3 mL)
  5. extractionThe organic extract
  6. concentrationis concentrated under reduced pressure to a volume of about 4 mL and tert-butyl methyl ether (8 mL in total)
  7. additionis slowly added
  8. additiondiluted with a small amount of isopropyl acetate
  9. stirringfurther stirred for 4.5 hours
  10. filtrationThe suspended, white solid is filtered
  11. washwashed with a small amount of isopropyl acetate
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-4f6fcbd7488f4a068fb49a305f2fd2c8
Source dataset
uspto-grants-2010_04
Patent number
US07700784B2

Reaction notes

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