3,4-dihydro-2H-pyran → 1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carbonitrile
Reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]#[N:7])[CH:3]=[N:2]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:20]1[CH:25]=[CH:24][CH2:23][CH2:22][CH2:21]1>C(Cl)Cl>[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[N:1]1[CH:5]=[C:4]([C:6]#[N:7])[CH:3]=[N:2]1Participants
Conditions
- Temperature
- 3 °C
Procedure
The reaction was carried out in a 3 liter three-necked flask with internal thermometer under argon. 50 g (537 mmol) of 1H-pyrazole-4-carbonitrile were suspended in 1.66 liter of methylene chloride and, after 3 h, cooled to 3° C. using an ice bath. At this temperature, 10.2 g (53.7 mmol) of 4-toluenesulphonic acid monohydrate were added. At 3° to 6° C., 58.8 ml (54.2 g, 644 mmol) of 3,4 dihydro-2H-pyran were then added dropwise over a period of 30 min. The reaction was then stirred at RT overnight. The clear reaction solution was then washed with 2 M aqueous sodium carbonate solution and with water, dried over magnesium sulphate, filtered and concentrated. The residue was triturated with cyclohexane and the solid obtained was filtered off with suction and dried in a vacuum drying cabinet at 30° C. for 4 h. This gave 91.8 g (96% of theory) of the title compound as a light-yellow powder.
Workup
- customThe reaction was carried out in a 3 liter three-necked flask with internal thermometer under argon
- washThe clear reaction solution was then washed with 2 M aqueous sodium carbonate solution and with water
- dry with materialdried over magnesium sulphate
- filtrationfiltered
- concentrationconcentrated
- customThe residue was triturated with cyclohexane
- customthe solid obtained
- filtrationwas filtered off with suction
- customdried in a vacuum
- customdrying cabinet at 30° C. for 4 h
Sources & evidence
- ORD record
- ord-c4bc2290b2e9446a903372f8f213356e
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394309B2
Reaction notes
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