Acetic Acid → 1-(5-amino-4-fluoro-2-hydroxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 1754425Notes

Reaction equation

HRID 1754425 reaction equation
[F:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([N:11]2[C:15](=[O:16])[N:14]([CH3:17])[N:13]=[N:12]2)=[C:4]([OH:18])[CH:3]=1.CCO.CC(O)=O.CC1C=C2N=C3C(=NC(NC3=O)=O)N(C[C@H](O)[C@H](O)[C@H](O)CO)C2=CC=1C>O.[Pd]>[NH2:8][C:7]1[C:2]([F:1])=[CH:3][C:4]([OH:18])=[C:5]([N:11]2[C:15](=[O:16])[N:14]([CH3:17])[N:13]=[N:12]2)[CH:6]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 702EthanolHCID 493570RiboflavinHCID 867044761-(4-fluoro-2-hydroxy-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one

Product 1

HCID 1363444071-(5-amino-4-fluoro-2-hydroxyphenyl)-4-methyl-1H-tetrazol-5(4H)-oneYield 99%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

A round-bottom flask was charged with 1-(4-fluoro-2-hydroxy-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (500 mg, 1.96 mmol), EtOH (20 mL), HOAc (250 uL), and 10% Pd/C (50% in water, Degussa type E101; 100 mg, 20 wt % by weight of the starting nitro compound). The flask was sealed with a rubber septum, degassed, and back-filled with H2 (×3) from a balloon filled with H2. The reaction was stirred for 2 h using a H2 filled balloon. The reaction mixture was filtered through a pad of celite, and the pad of celite was rinsed with MeOH. The filtrate was evaporated to dryness, and the product dried in vacuo with a water bath at 45° C. to remove any residual HOAc to provide 1-(5-amino-4-fluoro-2-hydroxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (437 mg, 99%) as a brown solid that was used without further purification. 1H NMR (300 MHz; d6-DMSO) δ 9.46 (s, 1H), 6.67-6.72 (m, 2H), 4.80 (bs, 2H), 3.56 (s, 3H); 19F NMR (282 MHz; d6-DMSO) δ −128.6 (t); m/z=225 (M+H)+.

Workup

  1. customThe flask was sealed with a rubber septum
  2. customdegassed
  3. additionback-filled with H2 (×3) from a balloon
  4. additionfilled with H2
  5. filtrationThe reaction mixture was filtered through a pad of celite
  6. washthe pad of celite was rinsed with MeOH
  7. customThe filtrate was evaporated to dryness
  8. customthe product dried in vacuo with a water bath at 45° C.
  9. customto remove any residual HOAc

Sources & evidence

ORD record
ord-d0a279c03bab4d8882c1feb73e158391
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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