1,2-Cyclohexanediol → 4-Chloro-6-(2-hydroxycyclohexyloxy)pyrimidine
Reaction equation
[H-].[Na+].[CH:3]1([OH:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[OH:9].[Cl:11][C:12]1[CH:17]=[C:16](Cl)[N:15]=[CH:14][N:13]=1.[Cl-].[NH4+]>O1CCCC1>[Cl:11][C:12]1[CH:17]=[C:16]([O:9][CH:4]2[CH2:5][CH2:6][CH2:7][CH2:8][CH:3]2[OH:10])[N:15]=[CH:14][N:13]=1Participants
Procedure
In 30 ml of tetrahydrofuran was suspended 1.78 g of sodium hydride (60% in oil), to which 3 ml of a tetrahydrofuran solution containing 2.35 g of 1,2-cyclohexanediol (mixture of cis-form and trans-form) was slowly added dropwise with stirring at room temperature. The mixture was stirred at room temperature for 10 minutes and then cooled to 0° C., to which 7 ml of a tetrahydrofuran solution containing 3 g of 4,6-dichloropyrimidine was slowly added dropwise, followed by further stirring at 0° C. for 3 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution and extracted three times with ethyl acetate. The organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 1.6 g of 4-chloro-6-(2-hydroxycyclohexyloxy)pyrimidine.
Workup
- additionwas slowly added dropwise
- stirringThe mixture was stirred at room temperature for 10 minutes
- additionwas slowly added dropwise
- stirringby further stirring at 0° C. for 3 hours
- extractionextracted three times with ethyl acetate
- washwashed with brine
- dry with materialdried over anhydrous magnesium sulfate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-983ef84057344271a3d6ba2331e3b870
- Source dataset
- uspto-grants-2007_11
- Patent number
- US07291730B2
Reaction notes
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