Ethyl bromoacetate → HCID 22034120, compound

HRID 2121581Notes

Reaction equation

HRID 2121581 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.[NH4+].[Cl-]>[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, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 25517Ammonium ChlorideSolvent2×

Conditions

Temperature
0 °C

Procedure

Slowly add dropwise ethyl bromoacetate (23 mL; 0.21 mol) 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). Stir the mixture for 1 day, pour into an aqueous NH4Cl solution (ca. 1 L), and extract with 3×200 mL of Et2O. Wash the combined extracts with saturated brine, dry over Na2SO4, filter, and concentrate in vacuo. Dissolve the residue in THF (200 mL), cool to 0° C., and add slowly in portions potassium t-butoxide (12 g; 0.11 mol) over a 10-minute period. After 30 minutes at 0° C., dilute the mixture with aqueous NH4Cl and extract with 2×150 mL of 50% Et2O in hexane. Wash the combined extracts with saturated brine, dry over Na2SO4, filter, concentrate in vacuo, and purify by column chromatography on silica gel (eluent: 5 to 10% EtOAc in hexane) to obtain the title compound as an oil: 1H NMR (400 MHz, CDCl3) δ 1.47 (t, 3H), 2.06 (s, 6H), 2.35 (s, 3H), 4.46 (br q, 2H), 6.6 (br t, 1H), 6.75 (d, 1H), 6.9 (br t, 1H), 7.00 (s, 2H), 9.4 (1H).

Workup

  1. extractionextract with 3×200 mL of Et2O
  2. washWash the combined extracts with saturated brine
  3. dry with materialdry over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. dissolutionDissolve the residue in THF (200 mL)
  7. waitAfter 30 minutes at 0° C.
  8. extractionextract with 2×150 mL of 50% Et2O in hexane
  9. washWash the combined extracts with saturated brine
  10. dry with materialdry over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate in vacuo
  13. custompurify by column chromatography on silica gel (eluent: 5 to 10% EtOAc in hexane)

Sources & evidence

ORD record
ord-880f5515f8f34e179b1b33b7371d2a6e
Source dataset
uspto-grants-2004_02
Patent number
US06696445B2

Reaction notes

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