Azetidine → ethyl 4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxylate
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:10]([CH3:11])[N:9]=[CH:8][C:7]=1[C:12]([OH:14])=O)=[O:5])[CH3:2].C([N:17]([CH:21]([CH3:23])C)[CH:18](C)C)C.N1CCC1>C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:10]([CH3:11])[N:9]=[CH:8][C:7]=1[C:12]([N:17]1[CH2:18][CH2:23][CH2:21]1)=[O:14])=[O:5])[CH3:2]Participants
Procedure
To a cooled solution of 5-(ethoxycarbonyl)-1-methyl-1H-pyrazole-4-carboxylic acid (1.5 g, 7.57 mmole), N-ethyldiisopropylamine (3.97 ml, 22.7 mmole) and azetidine (1.02 ml, 15.1 mmole) in ethyl acetate (30 ml) is added at 0° C. propanephosphonic acid cyclic anhydride (50% in ethyl acetate, 11.4 ml, 18.9 mole). The ice-bath is removed and the light yellow solution is stirred for 3 hr at room temperature. The light yellow solution is adjusted to pH 9 with sat. aqueous sodium carbonate solution, the aqueous layer is separated and extracted twice with ethyl acetate. The combined organic layer is washed with water and brine, dried with magnesium sulfate and the solvent is removed in vacuo affording 4-(azetidine-1-carbonyl)-2-methyl-2H-pyrazole-3-carboxylic acid ethyl ester (1.09 g, 60.7%) as a light brown viscous oil. MS: m/z=238.2 (M+H+).
Workup
- customThe ice-bath is removed
- customthe aqueous layer is separated
- extractionextracted twice with ethyl acetate
- washThe combined organic layer is washed with water and brine
- dry with materialdried with magnesium sulfate
- customthe solvent is removed in vacuo
Sources & evidence
- ORD record
- ord-c480684c942848068e1c5cd1e014f075
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349824B2
Reaction notes
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