Sodium hydride → HCID 86761730, compound

HRID 2194601Notes

Reaction equation

HRID 2194601 reaction equation
[OH:1][CH:2]1[CH2:5][O:4][CH2:3]1.[H-].[Na+].[H][H].[Br:10][C:11]1[C:12](Cl)=[N:13][C:14]([Cl:20])=[N:15][C:16]=1[CH2:17][O:18][CH3:19]>C1COCC1>[Br:10][C:11]1[C:16]([CH2:17][O:18][CH3:19])=[N:15][C:14]([Cl:20])=[N:13][C:12]=1[O:1][CH:2]1[CH2:5][O:4][CH2:3]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 9942117Oxetan-3-olHCID 86761728HCID 86761728, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 86761730HCID 86761730, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-hydroxyoxetane (76 mg, 1.02 mmol) in anhydrous THF (8 mL) at r.t. was added NaH (60% in mineral oil, 39 mg, 0.97 mmol). The mixture was stirred at r.t. for 5 min until there was no hydrogen bubbles generated. 5-bromo-2,4-dichloro-6-(methoxymethyl)pyrimidine (1) (250 mg, 0.93 mmol) was added and the resulting reaction mixture was stirred at r.t. overnight. The reaction was quenched with aqueous NH4Cl and extracted with EtOAc. The organic layer was separated, washed with aqueous NaHCO3, and dried (Na2SO4) and concentrated in vacuo. The residue was purified using ISCO chromatography (24 g silica gel, 0-20% EtOAc in hexanes in 40 min) to give the title compound (207 mg, 73%) as a white solid. 1H NMR (DMSO, 500 MHz) δ 5.57-5.52 (m, 1H), 4.91-4.86 (m, 2H), 4.68 (s, 2H), 4.61-4.57 (m, 2H), 3.98 (s, 3H).

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred at r.t. overnight
  3. customThe reaction was quenched with aqueous NH4Cl
  4. extractionextracted with EtOAc
  5. customThe organic layer was separated
  6. washwashed with aqueous NaHCO3
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified
  10. customISCO chromatography (24 g silica gel, 0-20% EtOAc in hexanes in 40 min)

Sources & evidence

ORD record
ord-3b856de03f714facba1b54b04866c6c7
Source dataset
uspto-grants-2012_12
Patent number
US08334292B1

Reaction notes

Loading…