Diiodomethane → HCID 86631946, compound

HRID 906137Notes

Reaction equation

HRID 906137 reaction equation
N[C:2]1[C:3]([CH3:20])=[C:4]([CH:12]=[C:13]([CH3:19])[C:14]=1[C:15]([O:17][CH3:18])=[O:16])[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[I:21]CI.N(OCCC(C)C)=O>C1COCC1.[Cu]I>[I:21][C:2]1[C:3]([CH3:20])=[C:4]([CH:12]=[C:13]([CH3:19])[C:14]=1[C:15]([O:17][CH3:18])=[O:16])[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6]

Participants

6

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 86631945HCID 86631945, compound

Product 1

HCID 86631946HCID 86631946, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

1-tert-Butyl 4-methyl 3-amino-2,5-dimethylterephthalate (0.444 g, 1.59 mmol) was dissolved in THF (10 mL), and the mixture was sparged with nitrogen for 10 minutes. Copper (I) iodide (302 mg, 1.59 mmol) and diiodomethane (0.64 mL, 7.93 mmol) were added followed by isoamyl nitrite (0.63 mL, 4.74 mmol), and the mixture was stirred at reflux for 20 h. The mixture was cooled to ambient temperature and then was partitioned between ethyl acetate and 1N hydrochloric acid. The aqueous portion was extracted with ethyl acetate (2×). The combined organic portion was washed with brine, dried over sodium sulfate, then filtered and concentrated to provide an oil which was purified by column chromatography (silica gel, 2-10% ethyl acetate in hexanes). The clean fractions were combined and concentrated, and the residue was partitioned between ethyl acetate and 1: I saturated sodium bicarbonate solution: 1 M sodium thiosulfate. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, then filtered and concentrated to afford 1-tert-butyl 4-methyl 3-iodo-2,5-dimethylterephthalate (300 mg, 0.769 mmol, 48% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.42 (s, 1H), 3.96 (s, 3H), 2.60 (s, 3H), 2.31 (s, 3H), 1.59 (s, 9H); GCMS for C15H19IO4: 359 ([M-OCH3]+).

Workup

  1. customthe mixture was sparged with nitrogen for 10 minutes
  2. temperatureat reflux for 20 h
  3. customwas partitioned between ethyl acetate and 1N hydrochloric acid
  4. extractionThe aqueous portion was extracted with ethyl acetate (2×)
  5. washThe combined organic portion was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide an oil which
  10. customwas purified by column chromatography (silica gel, 2-10% ethyl acetate in hexanes)
  11. concentrationconcentrated
  12. customthe residue was partitioned between ethyl acetate and 1
  13. extractionThe aqueous portion was extracted with ethyl acetate
  14. washThe combined organic portion was washed with brine
  15. dry with materialdried over sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-822a044bde044cbcb5542e619dd61314
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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