Sodium → HCID 178439238, compound

HRID 2081574Notes

Reaction equation

HRID 2081574 reaction equation
[OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([CH2:11][CH3:12])[N:5]=[C:4]([C:13]([F:16])([F:15])[F:14])[N:3]=1.[Na].C[O-].[Na+].Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:35]2[N:39](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:38]=[N:37][N:36]=2)=[CH:25][CH:24]=1>CN(C=O)C>[CH2:11]([C:6]1[N:5]=[C:4]([C:13]([F:16])([F:14])[F:15])[N:3]=[C:2]([O:1][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[C:35]3[NH:36][N:37]=[N:38][N:39]=3)=[CH:25][CH:24]=2)[C:7]=1[CH2:8][CH2:9][CH3:10])[CH3:12]

Participants

6

Reactant 4

HCID 5360545Sodium2×HCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 10942334Sodium MethoxideHCID 178439771HCID 178439771, compound

Product 1

HCID 178439238HCID 178439238, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

4-Hydroxy-6-ethyl-5-propyl-2-(trifluoromethyl)pyrimidine (1.2 g, 5 mmole) was converted to the sodium salt with sodium methoxide (275 mg). The sodium salt was dissolved in DMF and mixed with 2.8 g (5 mmole) of 5-(4'-bromomethylbiphenyl-2-yl)-1-trityl-1H-tetrazole [U.S. Pat. No. 4,870,186], and the mixture heated at 50° C. for 18 hours. The solvent was evaporated to dryness and the residue was triturated with excess water to give a gum which was extracted into EtoAc. The organic layer was washed with H2O twice, dried over Na2SO4 and evaporated to a thick oil (4 g). One gram of this oil was treated with dry HCl saturated methanol for 3 hours then evaporated to dryness. The residue was triturated with hexane twice and decanted to afford a gum. The rest of the material was treated in the same way to provide a total of 2 g of crude product. Flash chromatography through silica gel and elution with CHCl3 contg. 4% MeOH gave 210 mg of the desired compound as a white solid. TLC, Silica gel (CHCl3 -MeOH-NH4OH,7:3:2%) Rf 0.55 MS (DCI) [M+H]+ 469

Workup

  1. customThe solvent was evaporated to dryness
  2. customthe residue was triturated with excess water
  3. customto give a gum which
  4. extractionwas extracted into EtoAc
  5. washThe organic layer was washed with H2O twice
  6. dry with materialdried over Na2SO4
  7. customevaporated to a thick oil (4 g)
  8. additionOne gram of this oil was treated with dry HCl saturated methanol for 3 hours
  9. customthen evaporated to dryness
  10. customThe residue was triturated with hexane twice
  11. customdecanted
  12. customto afford a gum
  13. additionThe rest of the material was treated in the same way
  14. customto provide a total of 2 g of crude product
  15. washFlash chromatography through silica gel and elution with CHCl3 contg

Sources & evidence

ORD record
ord-6edb14eaff954501bb6716dfbec9d4b1
Source dataset
uspto-grants-1993_02
Patent number
US05185340

Reaction notes

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