Ethyl bromodifluoroacetate → Ethyl Difluoro(5-methylpyridin-2-yl)acetate

HRID 1987045Notes

Reaction equation

HRID 1987045 reaction equation
Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].Br[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]=1>CS(C)=O>[CH2:6]([O:5][C:3](=[O:4])[C:2]([F:9])([F:8])[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]=1)[CH3:7]

Participants

4

Reactant 2

HCID 69585Ethyl bromodifluoroacetateHCID 5642162-Bromo-5-methylpyridine

Product 1

HCID 12035972Ethyl Difluoro(5-methylpyridin-2-yl)acetateYield 56%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred suspension of Cu(0) (12.2 g, 0.19 mmol, 2.2×) in DMSO (87 mL) at RT under argon was added ethyl bromodifluoroacetate (13.4 mL, 0.10 mol, 1.2×) (see Eto, H., et al.; Chem. Pharm. Bull. 48: 982-990, 2000; and Ashwood, M. S., et al.; Tetrahedron Lett. 43: 9271-9273, 2002). After 2.5 h, 2-bromo-5-methylpyridine was added in one portion, the flask resealed, re-evacuated, and purged with argon. After 48 h, the reaction was partitioned between EtOAc (200 mL) and saturated NH4Cl (150 mL). The organic phase was rewashed with saturated NH4Cl (100 mL) until the blue color dissipated. The organic phase was dried over Na2SO4 and concentrated in vacuo to afford a yellow/green non-viscous oil. Purification via flash chromatography (30% EtOAc/hexanes) afforded the product as a clear oil (10.5 g, 0.05 mol, 56% yield). 1H NMR (300 Hz, CDCl3) δ 8.47 (s, 1H), 7.63 (m, 2H), 4.37 (q, J=7.3 Hz), 2.40 (s, 3H), 1.33 (t, J=7.3 Hz, 3H); LC/MS (m/z) [M+1]+ 216.2 (calculated for C10H12F2NO2, 216.2).

Workup

  1. customre-evacuated
  2. custompurged with argon
  3. waitAfter 48 h
  4. customthe reaction was partitioned between EtOAc (200 mL) and saturated NH4Cl (150 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow/green non-viscous oil
  8. customPurification via flash chromatography (30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-bd39a4ff1e2a45ba9bdf648eb6594016
Source dataset
uspto-grants-2009_06
Patent number
US07550474B2

Reaction notes

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