Benzyl 2,2,2-trichloroacetimidate → methyl 3-(benzyloxy)-3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethylpropanoate

HRID 563418Notes

Reaction equation

HRID 563418 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([OH:25])[C:18]([CH3:24])([CH3:23])[C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH2:26](OC(=N)C(Cl)(Cl)Cl)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl.C(S(O)(=O)=O)(F)(F)F.[Cl-].[Na+].O>[CH2:26]([O:25][CH:17]([C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[N:9]=[CH:10]2)[C:18]([CH3:23])([CH3:24])[C:19]([O:21][CH3:22])=[O:20])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 2

HCID 144968Benzyl 2,2,2-trichloroacetimidate2×HCID 67005676methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-hydroxy-2,2-dimethylpropanoate

Product 1

HCID 59252793methyl 3-(benzyloxy)-3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethylpropanoateYield 15%

Reagents, catalysts & solvents 3

HCID 62406Trifluoromethanesulfonic acidCatalystHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-hydroxy-2,2-dimethylpropanoate (282 mg, 0.82 mmol) was dissolved in 10 mL DCM and benzyl-2,2,2-trichloroacetimidate (0.185 mL, 1.0 mmol) was added followed by 3 drops of CF3SO3H. The reaction was stirred for 2 h. Reaction was incomplete so added more benzyl-2,2,2-trichloroacetimidate (0.185 mL, 1.0 mmol). After 12 h, diluted with brine and extracted with DCM×3. The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by SiO2 chromatography eluting with EtOAc/hexane gradient. Obtained 52 mg (15% yield) of methyl 3-(benzyloxy)-3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethylpropanoate. MS found: (M+H)+=433.

Workup

  1. customReaction
  2. waitAfter 12 h
  3. extractionextracted with DCM×3
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by SiO2 chromatography
  8. washeluting with EtOAc/hexane gradient

Sources & evidence

ORD record
ord-c6bbfbfa994e412d860b4e9fd463b8a9
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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