Isopropyl iodide → Ethyl 3,3-bis(4-fluorophenyl)-2-[2-(1-methylethyl) 2H-tetrazol-5-yl]-2-propenoate

HRID 330634Notes

Reaction equation

HRID 330634 reaction equation
C(=O)=O.[CH3:4][C:5]([CH3:7])=O.[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[C:16]([C:22]2[NH:26][N:25]=[N:24][N:23]=2)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:11][CH:10]=1.[H-].[Na+].IC(C)C>CN(C)C=O>[F:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]([C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)=[C:16]([C:22]2[N:23]=[N:24][N:25]([CH:5]([CH3:7])[CH3:4])[N:26]=2)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 18522661Acetone cardiceHCID 178470939HCID 178470939, compound

Product 1

HCID 14723868Ethyl 3,3-bis(4-fluorophenyl)-2-[2-(1-methylethyl) 2H-tetrazol-5-yl]-2-propenoateYield 56.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

To a chilled (-78° C., dry ice-acetone) solution of ethyl 3,3-bis(4-fluorophenyl)-2-(1-H-tetrazol-5-yl)-2-propenoate (2.6 g, 7.3 mmoles) [prepared in Example 2] in 20 mL of dried N,N-dimethylformamide under argon was added NaH (0.44 g, 11.0 mmoles; 60% in mineral oil) followed by reagent grade 2-iodopropane (2.0 mL, 20.0 mmoles) in one single portion. The thick reaction mixture was stirred under argon at -78° C. for 30 minutes and the mixture was allowed to warm to room temperature slowly over a period of 16 hours. Analytical TLC eluted once with 50% ethyl acetate in hexanes showed only one spot at Rf =0.86. The white suspension was diluted with 40 mL of half saturated brine followed by 20 mL of ethyl acetate. The aqueous layer was washed with ethyl acetate (2×20 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. Analytical TLC eluted four times with 8% (v/v) ethyl acetate in hexanes showed two spots at Rf =0.38(21) and Rf =0.49 (21a). The desired products were purified by silica gel column chromatography eluted with 8% EtOAc in hexanes. The fast moving product was collected to give 1.64 g (56.5%) of the title compound. MS (CI): m/e=399 for (M+H)+ ;

Workup

  1. temperatureto warm to room temperature slowly over a period of 16 hours
  2. washAnalytical TLC eluted once with 50% ethyl acetate in hexanes
  3. additionThe white suspension was diluted with 40 mL of half saturated brine
  4. washThe aqueous layer was washed with ethyl acetate (2×20 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. washAnalytical TLC eluted four times with 8% (v/v) ethyl acetate in hexanes
  8. customThe desired products were purified by silica gel column chromatography
  9. washeluted with 8% EtOAc in hexanes
  10. customwas collected

Sources & evidence

ORD record
ord-542a7bcf01b046d3b27834b2729173c5
Source dataset
uspto-grants-1990_01
Patent number
US04897490

Reaction notes

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