Ethyl bromoacetate → HCID 22034120, compound

HRID 2299261Notes

Reaction equation

HRID 2299261 reaction equation
Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[N:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH:14]([C:17]1[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[CH:19][C:18]=1[CH3:25])[C:15]#[N:16].C(=O)([O-])[O-].[K+].[K+].CC(C)([O-])C.[K+]>CS(C)=O.[Cl-].[NH4+]>[NH2:16][C:15]1[C:14]([C:17]2[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[CH:19][C:18]=2[CH3:25])=[C:9]2[N:8]([C:2]=1[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:13]=[CH:12][CH:11]=[CH:10]2

Participants

7

Reactant 4

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 220341262-(2-Pyridinyl)-2-(2,4,6-trimethylphenyl)ethanenitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 22034120HCID 22034120, compoundYield 63.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 25517Ammonium ChlorideSolvent2×

Conditions

Temperature
0 °C

Procedure

Ethyl bromoacetate (23 mL; 0.21 mol) is added slowly dropwise over a 3-hour period to a mixture of 2-(2-pyridinyl)-2-(2,4,6-trimethylphenyl)-ethanenitrile (22.3 g; 0.094 mol) and potassium carbonate (78 g; 0.57 mol) suspended in DMSO (100 mL). The mixture is stirred for 1 day, poured into an aqueous ammonium chloride solution (ca. 1 L), and extracted with three 200 mL portions of ethyl ether. Combined extracts are washed with saturated brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue is dissolved in THF (200 mL), cooled to 0° C., and potassium t-butoxide (12 g; 0.11 mol) is added slowly in portions over a 10-minute period. After 30 minutes at 0° C., the mixture is diluted with aqueous ammonium chloride and extracted twice with 150 mL portions of 50% ethyl ether in hexane. The combined extracts are washed with saturated brine, dried (Na2SO4), filtered, concentrated in vacuo, and chromatographed (5 to 10% ethyl acetate in hexane) to give 19.2 g of the title compound as an oil (63%): 1H nmr (400 MHz, CDCl3) d 1.47 (t, 3 H), 2.06 (s, 6 H), 2.35 (s, 3 H), 4.46 (br q, 2 H), 6.6 (br t, 1 H), 6.75 (d, 1 H), 6.9 (br t, 1 H), 7.00 (s, 2 H), 9.4 (br 1 H).

Workup

  1. extractionextracted with three 200 mL portions of ethyl ether
  2. washCombined extracts are washed with saturated brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue is dissolved in THF (200 mL)
  7. waitAfter 30 minutes at 0° C.
  8. extractionextracted twice with 150 mL portions of 50% ethyl ether in hexane
  9. washThe combined extracts are washed with saturated brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customchromatographed (5 to 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-016b69bb770848f4abe132b9bacf96cc
Source dataset
uspto-grants-2002_12
Patent number
US06495686B2

Reaction notes

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