Carbon Dioxide → N-[4-(2-Pyridylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamide

HRID 865074Notes

Reaction equation

HRID 865074 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]([C:8]([F:11])([F:10])[F:9])([OH:7])[C:4](O)=[O:5].C(=O)=O.[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]([C:25]1[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=1)=[O:24].C(N1C=CN=C1)(N1C=CN=C1)=O>O1CCCC1>[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]([C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:4](=[O:5])[C:3]([OH:7])([C:8]([F:11])([F:10])[F:9])[C:2]([F:13])([F:12])[F:1])=[CH:27][CH:26]=1)=[O:24]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 682631,1'-CarbonyldiimidazoleHCID 27250433,3,3-Trifluoro-2-hydroxy-2-(trifluoromethyl)propionic AcidHCID 10726619(4-Aminophenyl)-2-pyridinylmethanone

Product 1

HCID 21480152N-[4-(2-Pyridylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamideYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
43 °C

Procedure

Tetrahydrofuran (15 ml, dry) was added to a mixture of 2,2-bis-trifluoromethyl-2-hydroxyacetic acid (1.08 g, 5.1 mmol) and 1,1-carbonyldiimidazole (0.83 g, 5.1 mmol) while under a nitrogen atmosphere. There was an immediate evolution of carbon dioxide. The reaction was placed in an ultrasound bath at 23° C. for 15 min. The reaction was treated with 4-(2-pyridylcarbonyl)benzeneamine (1.01 g, 5.1 mmol), and heated to 43° C. in an ultrasound bath for 48 hr. The incomplete reaction was treated with a solid mixture of 2,2-bis-tri-fluoromethyl-2-hydroxyacetic acid (0.22 g, 1.04 mmol) and 1,1'-carbonyldiimidazole (0.20 g, 1.2 mmol) and heated to 53° C. in an ultrasound bath for 72 hr. The reaction was evaporated to a gold oil, which was treated with water (100 ml) and extracted with ethyl acetate (2×100 ml). the combined organic portions were dried (MgSO4) and evaporated to a gold oil. Chromatography of this oil on silica gel eluting with methylenechloride/ethyl acetate (first 100:0 and then 85:15) provided a tan solid (0.37 g, 19%); mp 197°-200° C. 1H-NHR (250 MHz, d6 -DMSO): 7.68 (m, 1H, ArH), 8.00 (m, 6H, ArH), 8.74 (d, J=4.33, 1H, ArH), 9.93 (br s, 1H, OH), 10.83 (br s, 1H, NH). MS(CI,CH4): 393 (M+1).

Workup

  1. customThe incomplete reaction
  2. temperatureheated to 53° C. in an ultrasound bath for 72 hr
  3. customThe reaction was evaporated to a gold oil, which
  4. additionwas treated with water (100 ml)
  5. extractionextracted with ethyl acetate (2×100 ml)
  6. dry with materialthe combined organic portions were dried (MgSO4)
  7. customevaporated to a gold oil

Sources & evidence

ORD record
ord-fa70dc7ee708400098ac017c1f0f8568
Source dataset
uspto-grants-1996_10
Patent number
US05565465

Reaction notes

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