Sodium hydride → HCID 10410270, compound

HRID 719550Notes

Reaction equation

HRID 719550 reaction equation
[CH2:1]([C:5]1[N:9]=[C:8]([C:10]([F:15])([F:14])[CH2:11][CH2:12][CH3:13])[NH:7][N:6]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[H][H].Br[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([O:36]C)=[O:35])=[CH:24][CH:23]=1>CN(C)C=O.CO>[CH2:1]([C:5]1[N:6]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[C:29]([C:34]([OH:36])=[O:35])=[CH:30][CH:31]=[CH:32][CH:33]=3)=[CH:24][CH:23]=2)[N:7]=[C:8]([C:10]([F:14])([F:15])[CH2:11][CH2:12][CH3:13])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 11012181Methyl 4'-(bromomethyl)biphenyl-2-carboxylateHCID 178418361HCID 178418361, compoundHCID 178441974HCID 178441974, compound

Product 1

HCID 10410270HCID 10410270, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

Under a static nitrogen atmosphere, 2.0 g (9.2 mmol) of solid 3-butyl-5-(1,1-difluorobutyl)-1H-1,2,4-triazole is added in small portions to 10 mmol of sodium hydride in 50 ml of dimethylformamide (DMF); stirring is continued until hydrogen evolution has ceased. The anion solution is cooled to −10° C. (ice/methanol) and is treated with a solution of 3.0 g (9.2 mmol) of 4-bromomethyl-2′-methoxycarbonylbiphenyl (from Step 1 of Example 1) in 20 ml of dry DMF. The reaction is allowed to warm to ambient temperature and stir overnight. Methanol (10 ml) is added to destroy any unreacted sodium hydride and the DMF is removed in vacuo; the residue is dissolved in ethyl acetate, washed with water, and dried (MgSO4). Silica gel chromatography separates the two isomers; the more abundant isomer is dissolved in 80 ml of ethanol and is treated with 80 ml of 10% NaOH at ambient temperature for 3 days. The ethanol is removed in vacuo and the aqueous phase is acidified to pH 1 with hydrochloric acid which causes the product to precipitate; filtration and drying in vacuo gives 4′-[(5-butyl-3-(1,1-difluorobutyl)-1H-1,2,4-triazol-1-yl)methyl][1,1′-biphenyl)-2-carboxylic acid.

Workup

  1. stirringstir overnight
  2. customto destroy any unreacted sodium hydride
  3. customthe DMF is removed in vacuo
  4. dissolutionthe residue is dissolved in ethyl acetate
  5. washwashed with water
  6. dry with materialdried (MgSO4)
  7. dissolutionthe more abundant isomer is dissolved in 80 ml of ethanol
  8. additionis treated with 80 ml of 10% NaOH at ambient temperature for 3 days
  9. customThe ethanol is removed in vacuo
  10. customto precipitate
  11. filtrationfiltration
  12. customdrying in vacuo

Sources & evidence

ORD record
ord-e2d4af8c26574835b8a03985c8ae447d
Source dataset
uspto-grants-2006_11
Patent number
US07132437B2

Reaction notes

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