Reaction equation
[H-].[Na+].[CH2:3]([OH:7])[C:4]#[C:5][CH3:6].Cl[C:9]1[CH:14]=[C:13]([N:15]2[CH2:20][CH:19]([CH2:21][CH3:22])[CH2:18][CH:17]([CH2:23][CH3:24])[CH2:16]2)[N:12]=[CH:11][N:10]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:3]([O:7][C:9]1[CH:14]=[C:13]([N:15]2[CH2:16][CH:17]([CH2:23][CH3:24])[CH2:18][CH:19]([CH2:21][CH3:22])[CH2:20]2)[N:12]=[CH:11][N:10]=1)[C:4]#[C:5][CH3:6]Participants
Procedure
0.16 g of sodium hydride (60% oil suspension) was suspended in 4 ml of tetrahydrofuran. 1 ml of tetrahydrofuran solution of 0.27 g of 2-butyn-1-ol was added dropwise therein, and the mixture was stirred for 10 minutes at room temperature. Into the mixture was added dropwise 1 ml of tetrahydrofuran solution of 0.64 g of 4-chloro-6-(3,5-diethylpiperidino)pyrimidine, wherein the ratio of cis/trans diastereomer on the piperidino ring was 1:1, and stirred for 5 hours at 60° C. Into the reaction mixture was added a saturated ammonium chloride aqueous solution, and the mixture was extracted with tert-butyl methyl ether three times. The organic layers were washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.41 g of 4-(2-butynyloxy)-6-(3,5-diethylpiperidino)pyrimidine (hereinafter, referred to as Compound (30)). Compound (30) had the cis/trans diastereomer originated two ethyls on the pyperidine ring. The ratio of the cis/trans diastereomer was about 1/1.
Workup
- stirringstirred for 5 hours at 60° C
- extractionthe mixture was extracted with tert-butyl methyl ether three times
- washThe organic layers were washed with a saturated sodium chloride aqueous solution
- dry with materialdried over anhydrous magnesium sulfate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-63d1240576d545a0996dc55457f0195a
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07732448B2
Linked notes
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