Pyridine → 3[-(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol

HRID 378845Notes

Reaction equation

HRID 378845 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:25])=[C:6]([CH2:8][N:9]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[O:11][C:10]2=O)[CH:7]=1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.N1C=CC=CC=1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:25])=[C:6]([CH2:8][N:9]2[N:13]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=3)[O:11][CH2:10]2)[CH:7]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 10474339Bms-191011

Product 1

HCID 696770833[-(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one (740 mg, 2 mmol), p-nitrophenyl chloroformate (407 mg, 2.02 mmol), and pyridine (330 mg, 4.17 mmol) in anhydrous dichloromethane (20 mL) was stirred at room temperature for three hours. The corresponding aminoacid tert-butyl ester (2 mmol) and anhydrous triethylamine (405 mg, 4 mmol) were added and the resulting reaction mixture was stirred at room temperature overnight. After evaporation, the residue was partitioned between diethylether and dilute NaOH. The organic layer was washed with water, dilute HCl, and brine, and then dried over magnesium sulfate. The crude product was purified by either trituration or recrystallization. The tert-butyl ester was stirred in dichloromethane (5 mL) with trifluoroacetic acid (1 mL) at room temperature overnight. After evaporation of CH2Cl2 and excess TFA, the residue was recrystallized from benzene-acetone to afford pure desired product.

Workup

  1. customthe resulting reaction mixture
  2. customAfter evaporation
  3. customthe residue was partitioned between diethylether and dilute NaOH
  4. washThe organic layer was washed with water, dilute HCl, and brine
  5. dry with materialdried over magnesium sulfate
  6. customThe crude product was purified by either trituration or recrystallization
  7. stirringThe tert-butyl ester was stirred in dichloromethane (5 mL) with trifluoroacetic acid (1 mL) at room temperature overnight
  8. customAfter evaporation of CH2Cl2 and excess TFA
  9. customthe residue was recrystallized from benzene-acetone

Sources & evidence

ORD record
ord-8e41c36201624d4fa89f3eb323f76f29
Source dataset
uspto-grants-2001_10
Patent number
US06297241B1

Reaction notes

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