Sodium Hydroxide → 2-chloro-4-cyclopropyl-5-fluoroPyrimidine

HRID 634232Notes

Reaction equation

HRID 634232 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.CC(N)[CH2:12][C:13]1[CH:18]=CC=CC=1.OP(O)(O)=O.[Br-].C1([Zn+])CC1.[OH-].[Na+]>>[Cl:1][C:2]1[N:7]=[C:6]([CH:18]2[CH2:13][CH2:12]2)[C:5]([F:9])=[CH:4][N:3]=1

Participants

5

Reactant 4

HCID 14798Sodium HydroxideHCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 178419765HCID 178419765, compound

Product 1

HCID 772310692-chloro-4-cyclopropyl-5-fluoroPyrimidineYield 2,031.8%

Conditions

Temperature
70 °C

Procedure

In a 20 mL glass microwave tube 2,4-dichloro-5-fluoropyrimidine (500 mg, 2.99 mmol) and Amphos (53.0 mg, 0.075 mmol) were treated with 0.5 M cyclopropylzinc(II) bromide (7786 μL, 3.89 mmol) via syringe under an atmosphere of argon. The solution was then heated in the microwave at 70° C. for 20 min. The mixture was treated with 1N NaOH and extracted with EtOAc (25 mL), dried over MgSO4, filtered and concentrated. Purification with flash chromatography (eluting with 100% DCM) afforded 2-chloro-4-cyclopropyl-5-fluoropyrimidine (263 mg, 51%) as a pale yellow viscous oil. MS (ESI, pos. ion) m/z: 173.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.21-8.28 (1H, m), 2.24-2.34 (1H, m), 1.27-1.34 (2H, m), 1.17-1.27 (2H, m).

Workup

  1. extractionextracted with EtOAc (25 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification
  6. washwith flash chromatography (eluting with 100% DCM)

Sources & evidence

ORD record
ord-d4a753a62c97414ab547548efa56b47a
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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