Methanol → 1-(5-amino-4-fluoro-2-(1-hydroxy-2-methylpropan-2-yloxy)phenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 1754450Notes

Reaction equation

HRID 1754450 reaction equation
[NH2:1][C:2]1[C:16]([F:17])=[CH:15][C:5]([O:6][C:7]([CH3:14])([CH3:13])[C:8](OCC)=[O:9])=[C:4]([N:18]2[C:22](=[O:23])[N:21]([CH3:24])[N:20]=[N:19]2)[CH:3]=1.[BH4-].[Li+].CO.[OH-].[Na+]>CCOCC>[NH2:1][C:2]1[C:16]([F:17])=[CH:15][C:5]([O:6][C:7]([CH3:13])([CH3:14])[CH2:8][OH:9])=[C:4]([N:18]2[C:22](=[O:23])[N:21]([CH3:24])[N:20]=[N:19]2)[CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 86704492ethyl 2-(4-amino-5-fluoro-2-(4-methyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)phenoxy)-2-methylpropanoate

Product 1

HCID 867044931-(5-amino-4-fluoro-2-(1-hydroxy-2-methylpropan-2-yloxy)phenyl)-4-methyl-1H-tetrazol-5(4H)-oneYield 94%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 2-(4-amino-5-fluoro-2-(4-methyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)phenoxy)-2-methylpropanoate (5.60 g, 16.5 mmol, 1.00 equiv) in Et2O (155 mL) under argon was cooled to 0° C. The ice-cooled solution was charged with lithium borohydride (791 mg, 36.3 mmol, 2.20 equiv) followed by MeOH (1.540 mL), which resulted in the formation of a free-flowing precipitate. The reaction was stirred at 0° C. for 30 min, then the ice-bath was removed, and the reaction was stirred at ambient temperature for 1 h. At ambient temperature, the reaction was slowly quenched with aqueous 1 N NaOH (100 mL, 100 mmol, 6.00 equiv), which dissolved the free-flowing precipitate. The layers were separated, and the aqueous layer was extracted with DCM 2×. The organic layer was dried over Na2SO4, filtered, and concentrated to dryness to give 1-(5-amino-4-fluoro-2-(1-hydroxy-2-methylpropan-2-yloxy)phenyl)-4-methyl-1H-tetrazol-5(4H)-one (4.60 g, 94%) as a white solid that was used without further purification.

Workup

  1. customresulted in the formation of a free-flowing precipitate
  2. customthe ice-bath was removed
  3. stirringthe reaction was stirred at ambient temperature for 1 h
  4. dissolutiondissolved the free-flowing precipitate
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with DCM 2×
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-f588aac894a049a18968604bc5de3591
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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