Nitromethane → 3-[3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-1H-indole-6-carboxylic acid methyl ester

HRID 2224654Notes

Reaction equation

HRID 2224654 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=2)[CH:3]=[CH:2]1.Cl[Sn](Cl)(Cl)Cl.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:30]([C:31](Cl)=[O:32])=[C:29]([CH3:34])[O:28][N:27]=2)=[CH:22][CH:21]=1.[N+](C)([O-])=O>C(Cl)Cl>[CH3:13][O:12][C:10]([C:7]1[CH:8]=[C:9]2[C:4]([C:3]([C:31]([C:30]3[C:26]([C:23]4[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=4)=[N:27][O:28][C:29]=3[CH3:34])=[O:32])=[CH:2][NH:1]2)=[CH:5][CH:6]=1)=[O:11]

Participants

6

Reactant 4

HCID 6375NitromethaneHCID 24287Tin tetrachlorideHCID 639844Methyl indole-6-carboxylateHCID 27807113-(4-Fluorophenyl)-5-methyl-4-isoxazolecarbonyl chloride

Product 1

HCID 691113023-[3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-1H-indole-6-carboxylic acid methyl esterYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 1.75 g (10 mmol) methyl indole-6-carboxylate (commercially available) in 15 mL of dry CH2Cl2 under argon at 0° C. was added 1.41 mL (12 mmol) of SnCl4 in one portion. After removing the ice-bath, the mixture was stirred for 40 min at room temperature and then 2.39 g (10 mmol) of 3-(4-fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid chloride (Prepared from the corresponding acid according to: J. Agric. Food Chem. 1995, 43, 219-228.) in 5 mL of CH2Cl2 was added at 0° C. followed by the addition of 15 mL of nitromethane in one portion. The mixture was stirred for 15 minutes at 0° C., after which 50 mL of ice-water was added to quench the reaction. The organic phase was separated and the aqueous solution was extracted with CH2Cl2 (2×20 mL). The combined extracts were washed with brine (30 mL), dried over Na2SO4, and evaporated to give 3.5 g of crude product (purity ˜30%, LCMS) as brown semi-solid. The crude product was further washed with ethyl acetate to give 0.85 g of the title compound in 23% yield as a light-yellow powder. (m/e): 379.2 (MH+; 100%).

Workup

  1. customAfter removing the ice-bath
  2. stirringThe mixture was stirred for 15 minutes at 0° C.
  3. customto quench
  4. customthe reaction
  5. customThe organic phase was separated
  6. extractionthe aqueous solution was extracted with CH2Cl2 (2×20 mL)
  7. washThe combined extracts were washed with brine (30 mL)
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customto give 3.5 g of crude product (purity ˜30%, LCMS) as brown semi-solid
  11. washThe crude product was further washed with ethyl acetate

Sources & evidence

ORD record
ord-99f3bfa78ca84b208fc690713c62fe89
Source dataset
uspto-grants-2008_05
Patent number
US07378435B2

Reaction notes

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