Ethyl Acetate → 5-Bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine

HRID 1042745

Reaction equation

HRID 1042745 reaction equation
[H-].[Na+].[O:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[OH:12])[CH2:4][CH3:5].[Br:13][C:14]1[C:15](Cl)=[N:16][C:17]([Cl:20])=[N:18][CH:19]=1.CCOC(C)=O>CN(C=O)C.CC#N>[Br:13][C:14]1[C:15]([O:12][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:3][CH2:4][CH3:5])=[N:16][C:17]([Cl:20])=[N:18][CH:19]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 667552-EthoxyphenolHCID 2899735-Bromo-2,4-dichloropyrimidine

Product 1

HCID 790765415-Bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a suspension of NaH (0.42 g 60% in mineral oil, 10.5 mmol) in DMF (8.0 mL) was slowly added 2-ethoxylphenol (1.34 g, 9.7 mmol) in MeCN (4.0 mL) at 0° C. under N2. After the addition, the reaction mixture was allowed to warm up to room temperature for 0.5 hour. 5-bromo-2,4-dichloropyrimidine (2.0 g, 8.8 mmol) in MeCN (16.0 mL) was slowly added and then the resulting reaction mixture was stirred at room temperature for 24 hour. EtOAc (120 mL) was added and washed with NaOH (30 mL, 0.5N) and brine (25×2 mL). The organic layer was dried with MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (10% to 30% EtOAc in Hexanes, gradient elution) to provide the 5-bromo-2-chloro-4-(2-ethoxyphenoxy)pyrimidine. MS m/z=330 [M+1]+. Calc'd for: C12H10BrClN2O2: 329

Workup

  1. customat 0° C.
  2. additionAfter the addition
  3. customthe resulting reaction mixture
  4. washwashed with NaOH (30 mL, 0.5N) and brine (25×2 mL)
  5. dry with materialThe organic layer was dried with MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (10% to 30% EtOAc in Hexanes, gradient elution)

Sources & evidence

ORD record
ord-ea489643db744541870091d3137221ac
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Linked notes

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