Citric Acid → 3-Bromo-1-(4-fluorophenyl)-1h-1,2,4-triazole

HRID 1180639Notes

Reaction equation

HRID 1180639 reaction equation
[Br:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.[C:7]([OH:10])(=[O:9])[CH3:8].[C:11](O)(=O)[CH3:12].[F:15][C:16]1[CH:21]=[CH:20][C:19]([Bi]([C:30]2[CH:35]=[CH:34][C:33](F)=[CH:32]C=2)C2C=CC(F)=CC=2)=[CH:18][CH:17]=1.[CH3:37]N(C)C(N(C)C)=N.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(OCC)(=O)C.O>[C:7]([O:10][CH2:11][CH3:12])(=[O:9])[CH3:8].[CH3:30][CH2:35][CH2:34][CH:33]([CH3:32])[CH3:37].[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:4]2[CH:5]=[N:6][C:2]([Br:1])=[N:3]2)=[CH:18][CH:17]=1

Participants

10

Reactant 4

HCID 311Citric AcidHCID 664601,1,3,3-TetramethylguanidineHCID 11966511Acetic acid;tris(4-fluorophenyl)bismuthaneHCID 178419478HCID 178419478, compound

Product 2

HCID 21882781Isohexane ethyl acetateYield 40%HCID 235711323-Bromo-1-(4-fluorophenyl)-1h-1,2,4-triazoleYield 45%

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 3-bromo-1,2,4-1H-triazole (prepared as described in Chemische Berichte 1967, 100, 2250) (1.0 g, 6.76 mmol), tri(4-fluorophenyl)bismuth diacetate (prepared by the method described in Synthetic Communications 1996, 4569) (4.53 g, 7.4 mmol), copper (II) acetate (0.25 g, 20 mol %) and N,N,N′,N′-tetramethylguanidine (1.7 mL, 13.5 mmol) in dry tetrahydrofuran (30 mL) was stirred at 50° C. under a balloon of air for 16 hr. The suspension was poured into water (100 mL) and 1M citric acid (30 mL) to give a suspension of pH 3-4. Ethyl acetate (100 mL) was added and the mixture was filtered through Celite®, washing the filter cake with ethyl acetate (100 mL). The two phases of the filtrate were separated and the organic layer was dried (Na2SO4) and concentrated. Flash column chromatography on silica gel, eluting with 25% then 40% ethyl acetate—isohexane, gave 1-(4-fluorophenyl)-3-bromo-1,2,4-1H-triazole as an off-white solid (0.74 g, 45%). δ (1H, 400 MHz, CDCl3) 7.18-7.24 (2H, m), 7.60-7.65 (2H, m), 8.37 (1H, s). MS (ES+) 242, 244 ([MH]+). Step 2: [6S,9R,11R] 2′,3′,4′,5,5′,6,7,8,9,10-Decahydro-2-(1-(4-fluorophenyl)-1,2,4-triazol-3-yl)-5′-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3′-[1,2,5]thiadiazole] 1′,1′-dioxide

Workup

  1. customprepared by the method
  2. customto give
  3. additiona suspension of pH 3-4
  4. filtrationthe mixture was filtered through Celite®
  5. washwashing the filter cake with ethyl acetate (100 mL)
  6. customThe two phases of the filtrate were separated
  7. dry with materialthe organic layer was dried (Na2SO4)
  8. concentrationconcentrated
  9. washFlash column chromatography on silica gel, eluting with 25%

Sources & evidence

ORD record
ord-a23892edaaf5417a80a37de2404fb7b0
Source dataset
uspto-grants-2007_10
Patent number
US07282513B2

Reaction notes

Loading…