Potassium Phosphate, Tribasic → 2-Chloro-4-cyclopropylpyrimidine

HRID 1804585Notes

Reaction equation

HRID 1804585 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH:9]1(B(O)O)[CH2:11][CH2:10]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:9]2[CH2:11][CH2:10]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 775312,4-DichloropyrimidineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 249019152-Chloro-4-cyclopropylpyrimidine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

Nitrogen gas was bubbled through a mixture of 2,4-dichloropyrimidine (1.49 g, 10 mmol), cyclopropaneboronic acid (0.86 g, 10 mmol) and K3PO4 (5.31 g, 25 mmol) in THF (50 ml) for 10 min. Pd(dppf)Cl2 (817 mg, 1 mmol) was added and the mixture heated at 90° C. in a sealed tube overnight. The mixture was cooled and partitioned between water and EtOAc, the organic layer washed with sat. NaCl, dried over MgSO4, filtered and evaporated. The residue purified by MPLC (Biotage Horizon: FLASH 25+M) eluent: 100% Hexanes (90 ml), gradient rising from 100% Hexanes to 20% EtOAc in Hexanes (900 ml), then 20% EtOAc in Hexanes (500 ml) to give 750 mg (48%) as an off-white solid. 1H NMR (CDCl3): 1.18 (m, 4H), 1.99 (m, 1H), 7.09 (d, J 5.1 Hz, 1H), 8.36 (d, J 5.1 Hz, 1H).

Workup

  1. temperatureThe mixture was cooled
  2. custompartitioned between water and EtOAc
  3. washthe organic layer washed with sat. NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue purified by MPLC (Biotage Horizon: FLASH 25+M) eluent
  8. custom20% EtOAc in Hexanes (500 ml) to give 750 mg (48%) as an off-white solid

Sources & evidence

ORD record
ord-4e64a1368e6c4133856a1f15ce289bd3
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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