Potassium Phosphate, Tribasic → Methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate

HRID 1483002Notes

Reaction equation

HRID 1483002 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([O:11][CH3:12])=[O:10])=[CH:4][N:3]=1.[CH:13]1(B(O)O)[CH2:15][CH2:14]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[N:7]=[C:6]([CH:13]2[CH2:15][CH2:14]2)[C:5]([C:9]([O:11][CH3:12])=[O:10])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 23156323Methyl 2,4-dichloropyrimidine-5-carboxylate

Product 1

HCID 83835308Methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylateYield 26%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2,4-dichloropyrimidine-5-carboxylate (852 mg, 4 mmol) and cyclopropylboronic acid (344 mg, 4 mmol) in THF (10 mL) was added K3PO4 (3.1 g, 12 mmol) followed by Pd(dppf)Cl2 (292 mg, 0.4 mmol) under N2. The mixture was refluxed for 4 h until the material was disappeared. The reaction mixture was cooled to rt. THF was removed under vacuum. Water (20 mL) was added and the mixture was extracted with EtOAc (20 mL×3). The organic layers were dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative TLC to afford methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate (220 mg, 26% yield) as a white solid.

Workup

  1. temperatureThe mixture was refluxed for 4 h until the material
  2. customTHF was removed under vacuum
  3. additionWater (20 mL) was added
  4. extractionthe mixture was extracted with EtOAc (20 mL×3)
  5. dry with materialThe organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-d0cce3dab607415b9fe2beb196dd331f
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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