5-Chloro-2-iodopyrimidine → Ethyl 3-(5-chloropyrimidin-2-yl)propanoate

HRID 1482877Notes

Reaction equation

HRID 1482877 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5](I)=[N:6][CH:7]=1.[Br-].[CH2:10]([O:12][C:13](=[O:17])[CH2:14][CH2:15][Zn+])[CH3:11]>C1COCC1.[Cl-].[NH4+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([CH2:15][CH2:14][C:13]([O:12][CH2:10][CH3:11])=[O:17])=[N:6][CH:7]=1

Participants

7

Reactant 2

HCID 299380055-Chloro-2-iodopyrimidineHCID 178471816HCID 178471816, compound

Product 1

HCID 118155027Ethyl 3-(5-chloropyrimidin-2-yl)propanoate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

5-Chloro-2-iodopyrimidine (4 g, 16.64 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.92 g, 1.66 mmol) were suspended in THF (83 mL). 3-Ethoxy-3-oxopropylzinc bromide (33.3 mL, 16.64 mmol) was added, and the resultant mixture was stirred at room temperature for 18 hours. The mixture was diluted with saturated ammonium chloride and water (1:1) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc:Hexanes) to give ethyl 3-(5-chloropyrimidin-2-yl)propanoate. MS ESI calcd for C9H12ClN2O2[M+H]+ 215. found 215. 1H NMR (500 MHz, DMSO-d6) δ 8.82 (s, 2H), 4.00 (q, J=7.1 Hz, 2H), 3.13 (t, J=6.9 Hz, 2H), 2.78 (t, J=6.9 Hz, 2H), 1.11 (t, J=7.1 Hz, 3H).

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel (EtOAc:Hexanes)

Sources & evidence

ORD record
ord-3ace5a00046a46a28ff19890d33d5de1
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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