Water → Ethyl difluoro(6-methylpyridazin-3-yl)acetate

HRID 1386805Notes

Reaction equation

HRID 1386805 reaction equation
[F:1][C:2]([F:9])(I)[C:3]([O:5][CH2:6][CH3:7])=[O:4].Br[C:11]1[N:12]=[N:13][C:14]([CH3:17])=[CH:15][CH:16]=1.O.[NH4+].[Cl-]>CS(C)=O.[Cu]>[F:1][C:2]([F:9])([C:11]1[N:12]=[N:13][C:14]([CH3:17])=[CH:15][CH:16]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

7

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 2737200Ethyl difluoro(iodo)acetateHCID 119590863-Bromo-6-methylpyridazine

Product 1

HCID 69558022Ethyl difluoro(6-methylpyridazin-3-yl)acetateYield 97.1%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 679Dimethyl SulfoxideSolvent2×

Procedure

This procedure is derived from the general method of T. Taguchi, et al. (Tetrahedron Lett., 1986,27,6103-6106). Ethyl difluoroiodoacetate (0.355 mL, 651 mg, 2.60 mmol) was added to a rapidly stirred suspension of copper powder (333 mg, 5.24 mmol) in DMSO (6.5 mL) at RT. After 50 min., 3-bromo-6-methylpyridazine (300 mg, 1.73 mmol) was added in DMSO (1.0 mL). After 20 h, the mixture was transferred to a separatory funnel containing water (25 mL) and saturated aq. NH4Cl (25 mL), and extracted with EtOAc (2×50 mL). The organic extracts were washed with saturated aq. NaCl, dried (Na2SO4), decanted, and evaporated. Purification by flash column chromatography on silica gel, eluting with 70:30 v/v hexanes/EtOAc, gave 363 mg of the title compound as an amber liquid. For the title compound: 1H NMR (500 MHz, CDCl3) δ 7.79 (d, J=9, 1H), 7.53 (d, J=9, 1H), 4.43 (q, J=7, 2H), 2.82 (s, 3H), 1.38 (t, J=7, 3H).

Workup

  1. waitAfter 20 h
  2. customthe mixture was transferred to a separatory funnel
  3. extractionextracted with EtOAc (2×50 mL)
  4. washThe organic extracts were washed with saturated aq. NaCl
  5. dry with materialdried (Na2SO4)
  6. customdecanted
  7. customevaporated
  8. customPurification by flash column chromatography on silica gel
  9. washeluting with 70:30 v/v hexanes/EtOAc

Sources & evidence

ORD record
ord-094ba5aab61a40feb5fb1d43e75f45c4
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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