Phosphorus oxychloride → 4-Chloro-6-(1,1-dimethylethyl)pyrimidine
Reaction equation
O[C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[N:5]=[CH:4][N:3]=1.P(Cl)(Cl)([Cl:14])=O>>[Cl:14][C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[N:5]=[CH:4][N:3]=1Participants
Procedure
Next, 4.7 g of 4-hydroxy-6-tert-butylpyrimidine obtained in Step 1 and 14 mL of phosphoryl chloride were put in a 50 mL three-neck flask, and the mixture was heated and refluxed for 1.5 hours. After the reflux, phosphoryl chloride was distilled off under reduced pressure. The obtained residue was dissolved in dichloromethane, and washed with water and then a saturated aqueous solution of sodium hydrogen carbonate. Anhydrate magnesium sulfate was added to the obtained organic layer for drying. This mixture was subjected to gravity filtration, and the filtrate was condensed to give a solid. This solid was purified by silica gel column chromatography. As a developing solvent, a mixed solvent of hexane and ethyl acetate in a ratio of 10:1 (v/v) was used. The obtained fraction was condensed to give 4-chloro-6-tert-butylpyrimidine (white solid, yield of 78%). A synthetic scheme of Step 2 is shown in (b-2) below.
Workup
- temperaturethe mixture was heated
- temperaturerefluxed for 1.5 hours
- distillationAfter the reflux, phosphoryl chloride was distilled off under reduced pressure
- dissolutionThe obtained residue was dissolved in dichloromethane
- washwashed with water
- additionAnhydrate magnesium sulfate was added to the obtained organic layer
- customfor drying
- filtrationThis mixture was subjected to gravity filtration
- customcondensed
- customto give a solid
- customThis solid was purified by silica gel column chromatography
- customcondensed
Sources & evidence
- ORD record
- ord-aa2aed35bde643a0b38d8cd2b54b88aa
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08889858B2
Reaction notes
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