Hexafluorophosphate → 2-Azido-4-(3-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide

HRID 1667675Notes

Reaction equation

HRID 1667675 reaction equation
[N:1]([C:4]1[S:5][C:6]([C:19]([OH:21])=O)=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[N:8]=1)=[N+:2]=[N-:3].C[N:23](C(N(C)C)=[N+]1C2C(=NC=CC=2)N=N1)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[Cl-].[NH4+]>CN(C)C=O>[N:1]([C:4]1[S:5][C:6]([C:19]([NH2:23])=[O:21])=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[N:8]=1)=[N+:2]=[N-:3]

Participants

7

Reactant 5

HCID 9886HexafluorophosphateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 866428022-Azido-4-(3-trifluoromethyl-phenyl)-thiazole-5-carboxylic acidHCID 178484285HCID 178484285, compound

Product 1

HCID 866428032-Azido-4-(3-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amideYield 83.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2.20 g (7.01 mmole) of 2-azido-4-(3-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid, 38 mL of dimethylformamide, 3.47 g (8.85 mmole) of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium, 3-oxide, hexafluorophosphate(1-) (1:1) and 3.75 mL (21.53 mmole) of ethyldiisopropylamine was stirred at room temperature for 23 minutes, then 0.5733 g (10.72 mmole) of ammonium chloride was added. The mixture was stirred for 2.25 hours, then concentrated under reduced pressure and partitioned between 300 mL of ethyl acetate and 75 mL of water. The ethyl acetate layer was washed twice with 60 mL of water, twice with 55 mL of saturated aqueous sodium bicarbonate, once with 50 mL of brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with ethyl acetate-hexanes (gradient 10:90-100-:0) to give 1.841 g 2-azido-4-(3-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid amide as a light yellow solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompartitioned between 300 mL of ethyl acetate and 75 mL of water
  3. washThe ethyl acetate layer was washed twice with 60 mL of water, twice with 55 mL of saturated aqueous sodium bicarbonate, once with 50 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with ethyl acetate-hexanes (gradient 10:90-100-:0)

Sources & evidence

ORD record
ord-1b75d78143bf4d98a6034b2c037b5ab2
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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