Ethyl Acetate → 1-[4-(1-Hydroxy-cyclopropyl)-pyridin-3-yl]-3-(3-trifluoromethyl-phenyl)-imidazolidin-2-one
Reaction equation
[CH3:1][CH2:2][Mg+].[Br-].C([O:7][C:8](=O)[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[N:15]1[CH2:19][CH2:18][N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=2)[C:16]1=[O:30])C.C(OCC)(=O)C>C(OCC)C.CCCCCC.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[OH:7][C:8]1([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N:15]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:28])([F:27])[F:29])[CH:21]=3)[C:16]2=[O:30])[CH2:2][CH2:1]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
2.5 M Solution of EtMgBr (0.8 mL, 1.974 mmol) was added drop wise to a solution of titanium(IV)isopropoxide (187.3 mg, 0.659 mmol) in diethyl ether (10 mL) for a period of 15 minutes at −78° C. under nitrogen atmosphere. The resulting mixture was stirred for 90 minutes. This was followed by the addition of 3-[2-oxo-3-(3-trifluoromethyl-phenyl)-imidazolidin-1-yl]-isonicotinic acid ethyl ester (I-36c: 125 mg, 0.329 mmol) in diethyl ether (3 mL) at −78° C. and continued stirring at room temperature overnight. The reaction was monitored by TLC (80% ethyl acetate in hexane). The reaction mixture was cooled and partitioned between ethyl acetate and 1N HCl. The organic layer was concentrated to yield crude product which was purified by preparative HPLC to afford 8 mg of the product (6% yield).
Workup
- stirringcontinued stirring at room temperature overnight
- temperatureThe reaction mixture was cooled
- custompartitioned between ethyl acetate and 1N HCl
- concentrationThe organic layer was concentrated
- customto yield crude product which
- customwas purified by preparative HPLC
Sources & evidence
- ORD record
- ord-3da47c49a2d84b09973261ce81f0737c
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09029399B2
Reaction notes
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