Acetic Acid → HCID 67293310, compound

HRID 1038803Notes

Reaction equation

HRID 1038803 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([CH:21]=[O:22])=[N:9][N:10]2[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])=[CH:6][CH:5]=1)([O-:3])=[O:2].CC(=CC)C.P([O-])(O)(O)=O.[Na+].Cl([O-])=O.[Na+].C[Si](C=[N+]=[N-])(C)C.C[C:46](O)=[O:47]>O.CC(O)(C)C>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:21]([O:47][CH3:46])=[O:22])=[N:9][N:10]2[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:19])[CH3:20])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 105532-Methyl-2-buteneHCID 167693TrimethylsilyldiazomethaneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86665092HCID 86665092, compound

Product 1

HCID 67293310HCID 67293310, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

6-Nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde (1.72 g, 5.35 mmol, Preparation #N.1) was added to a solution of 2-methyl-2-butene (2.0 M in THF, 26.8 mL, 53.5 mmol) and t-BuOH (48.2 mL) under N2. A solution of sodium dihydrogen phosphate (3.35 g, 27.9 mmol) and sodium chlorite (1.50 g, 16.6 mmol) in water (16.1 mL) was added and the mixture was stirred at rt for about 3 h. The mixture was concentrated under reduced pressure. DCM (50 mL) and aqueous 1 N HCl (20 mL) were added and the layers separated. The aqueous layer was extracted with DCM (15 mL). The combined organic layers were washed with brine (10 mL), dried over Na2CO3, filtered, and concentrated under vacuum. The solid was dissolved in a mixture of THF (64.3 mL) and MeOH (16.1 mL). (Trimethylsilyl)diazomethane (2 M in Et2O, 4.01 mL, 8.03 mmol) was added drop-wise. After about 2 h, AcOH (1 mL) was added and the mixture was stirred for about 14 h. The mixture was concentrated under reduced pressure. DCM (100 mL) was added and the mixture was washed with an aqueous solution of saturated NaHCO3 (25 mL) and the layers separated. The organic layer was washed with brine (10 mL), dried over Na2CO3, filtered and concentrated in vacuo. The residue was purified by column chromatography (80 g silica gel) eluting with 10 to 20% EtOAc/heptane to provide methyl 6-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate (1.66 g, 88%): LC/MS (Table 2, Method c) Rt=2.99 min.; MS m/z: 352 (M+H)+, 369 (M+H2O)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additionDCM (50 mL) and aqueous 1 N HCl (20 mL) were added
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted with DCM (15 mL)
  5. washThe combined organic layers were washed with brine (10 mL)
  6. dry with materialdried over Na2CO3
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. dissolutionThe solid was dissolved in a mixture of THF (64.3 mL) and MeOH (16.1 mL)
  10. waitAfter about 2 h
  11. stirringthe mixture was stirred for about 14 h
  12. concentrationThe mixture was concentrated under reduced pressure
  13. additionDCM (100 mL) was added
  14. washthe mixture was washed with an aqueous solution of saturated NaHCO3 (25 mL)
  15. customthe layers separated
  16. washThe organic layer was washed with brine (10 mL)
  17. dry with materialdried over Na2CO3
  18. filtrationfiltered
  19. concentrationconcentrated in vacuo
  20. customThe residue was purified by column chromatography (80 g silica gel)
  21. washeluting with 10 to 20% EtOAc/heptane

Sources & evidence

ORD record
ord-b44a05152251446bb8c5b63c57f9ca75
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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