1,2-Dimethoxyethane → methyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzoate

HRID 2207007Notes

Reaction equation

HRID 2207007 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)=[O:4].Br[C:15]1[N:19]=[CH:18][N:17]([C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=2)[N:16]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>C(Cl)Cl.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:30][C:27]([F:28])([F:29])[O:26][C:23]1[CH:22]=[CH:21][C:20]([N:17]2[CH:18]=[N:19][C:15]([C:8]3[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)=[N:16]2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 712094283-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole

Product 1

HCID 78210282methyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzoateYield 52.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with (4-(methoxycarbonyl)phenyl)boronic acid (70.1 mg, 0.390 mmol), 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (100 mg, 0.325 mmol), aqueous Na2CO3 (1 M, 1.298 mL, 1.298 mmol), and Pd(PPh3)4 (37.5 mg, 0.032 mmol). The reaction vial was capped and evacuated/backfilled with nitrogen gas (3×). DME (2 mL) was added, the vial was capped, heated at 100° C. for 15 minutes (min) in a Biotage Initiator® microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to RT, and diluted with CH2Cl2 (3 mL) and water. The organic and aqueous phase was separated with a phase separator, and the organics were concentrated in vacuo. Purification via flash column chromatography using EtOAc/hexanes as eluent yielded the title compound as a white solid (62 mg, 52%): 1H NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 8.28 (m, 2H), 8.15 (m, 2H), 7.81 (m, 2H), 7.41 (m, 2H), 3.96 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −58.02; ESIMS m/z 364 ([M+H]+).

Workup

  1. customThe reaction vial was capped and evacuated/backfilled with nitrogen gas (3×)
  2. customthe vial was capped
  3. temperatureThe reaction mixture was cooled to RT
  4. customThe organic and aqueous phase was separated with a phase separator
  5. concentrationthe organics were concentrated in vacuo
  6. customPurification via flash column chromatography

Sources & evidence

ORD record
ord-08159e3c5d204bda976eceb72a87bfc5
Source dataset
uspto-grants-2016_06
Patent number
US09376401B2

Reaction notes

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