Triphenylphosphine → HCID 17964824, compound

HRID 1723674Notes

Reaction equation

HRID 1723674 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.[CH3:10][N:11]1[C:15]([CH2:16]O)=[N:14][CH:13]=[N:12]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:7]=1)[O:8][CH2:16][C:15]1[N:11]([CH3:10])[N:12]=[CH:13][N:14]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 183421Phenol, 5-bromo-2-fluoro-HCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanol

Product 1

HCID 17964824HCID 17964824, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A cooled (0° C.) solution of 5-bromo-2-fluorophenol, (2-methyl-2H-[1,2,4]triazol-3-yl)methanol and triphenylphosphine in tetrahydrofuran was treated dropwise with diisopropyl azodicarboxylate over 10 min. The resulting mixture was stirred overnight and then acetic acid was added. The reaction mixture was evaporated to dryness and the residue was partitioned between ethyl acetate and 0.01N sodium hydroxide solution. The organic phase was washed with water and brine, dried over anhydrous magnesium sulphate and pre-adsorbed onto silica. Purification by flash column chromatography on silica gel, eluting with isohexane on a gradient of ethyl acetate (10-50%), led to product-containing fractions that were combined. The material was further purified by flash column chromatography on silica gel, eluting with dichloromethane containing 1% ammonia on a gradient of methanol (0.5-3%), to give 5-(5-bromo-2-fluoro-phenoxymethyl)-1-methyl-1H-[1,2,4]triazole as an off-white solid (2.1 g, 37%): δH (360 MHz, CDCl3) 4.01 (3H, s), 5.29 (2H, s), 6.96-6.99 (1H, m), 7.09-7.13 (1H, m), 7.29 (1H, dd, J 5 and 2), 7.88 (1H, s); m/z (ES+) 288 [MH+].

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. customthe residue was partitioned between ethyl acetate and 0.01N sodium hydroxide solution
  3. washThe organic phase was washed with water and brine
  4. dry with materialdried over anhydrous magnesium sulphate and pre-adsorbed onto silica
  5. customPurification by flash column chromatography on silica gel
  6. washeluting with isohexane on a gradient of ethyl acetate (10-50%)
  7. additionto product-containing fractions that
  8. customThe material was further purified by flash column chromatography on silica gel
  9. washeluting with dichloromethane containing 1% ammonia on a gradient of methanol (0.5-3%)

Sources & evidence

ORD record
ord-ebbd7e3adbbb4ccdb73ec92774d73f3b
Source dataset
uspto-grants-2009_02
Patent number
US07485640B2

Reaction notes

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