Hydrogen Bromide → 2-Bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionitrile

HRID 233283

Reaction equation

HRID 233283 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:9][CH2:10][C:11]2[N:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:14][C:15]=2[CH3:16])=[N:6][CH:7]=1.[BrH:23].N([O-])=O.[Na+].[C:28](#[N:31])[CH:29]=[CH2:30]>O.[Cu-]=O.CC(C)=O>[Br:23][CH:29]([CH2:30][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:9][CH2:10][C:11]2[N:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:14][C:15]=2[CH3:16])=[N:6][CH:7]=1)[C:28]#[N:31]

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 7855AcrylonitrileHCID 110877225-Amino-2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]pyridineHCID 23668193Sodium Nitrite

Product 1

HCID 109385272-Bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionitrileYield 48%

Reagents, catalysts & solvents 3

HCID 178419072HCID 178419072, compoundCatalystHCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

To a mixture of 5-amino-2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]pyridine (9.1 g), an aqueous solution of HBr (47%, 14.2 ml) and acetone (150 ml) was added dropwise, at temperature not exceeding 10° C. a solution of sodium nitrite (NaNO2) (2.33 g) in water (10 ml). The mixture was stirred for 30 minutes at 10° C., to which was added acrylonitrile (CH2 =CHCN) (12.1 ml). To the mixture was added, while stirring vigorously, copper(I) oxide (Cu2O) (0.1 g). The reaction mixture was stirred for further one hour at temperature ranging from 30° to 35° C., followed by concentration under reduced pressure. The concentrate was poured into water, which was made alkaline with a conc. ammonia water, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4), then the solvent was distilled off under reduced pressure. The residual oily product was subjected to a silica gel column chromatography. From the fractions eluted with ethyl acetate--hexane (1:1, v/v), was obtained 2-bromo-3-[2-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]-5-pyridyl]propionitrile (6.11 g, 48%), which was recrystallized from ethyl acetate--hexane to give colorless crystals, m.p.93°-94° C.

Workup

  1. customexceeding 10° C.
  2. additionTo the mixture was added
  3. stirringwhile stirring vigorously
  4. stirringThe reaction mixture was stirred for further one hour at temperature
  5. customranging from 30° to 35° C.
  6. concentrationfollowed by concentration under reduced pressure
  7. additionThe concentrate was poured into water, which
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe ethyl acetate layer was washed with water
  10. dry with materialdried (MgSO4)
  11. distillationthe solvent was distilled off under reduced pressure
  12. washFrom the fractions eluted with ethyl acetate--hexane (1:1

Sources & evidence

ORD record
ord-e61f7be9d7924046bc7d0b79ad900d0d
Source dataset
uspto-grants-1997_01
Patent number
US05591862

Linked notes

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