Tetrahydrofuran → N-(3,5-Difluoro-benzyl)-2-methyl-malonamic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:10])[CH:5]([CH3:9])[C:6]([OH:8])=O)[CH3:2].O1CCCC1.[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([F:25])[CH:24]=1)[CH2:20][NH2:21].Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>>[CH2:1]([O:3][C:4](=[O:10])[CH:5]([CH3:9])[C:6]([NH:21][CH2:20][C:19]1[CH:18]=[C:17]([F:16])[CH:24]=[C:23]([F:25])[CH:22]=1)=[O:8])[CH3:2]Participants
Reactant 5
Product 1
Procedure
To a solution of 2.92 g (20 mmol) methyl-malonic acid monoethyl ester in 100 ml of tetrahydrofuran 2.86 g (20 mmol) of 3,5-difluorobenzylamine, 3.83 g (20 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, 2.70 g (20 mmol) of 1-hydroxybenzotrizole hydrate and 2.58 g (20 mmol) of N,N-diisopropyl-ethylamine were added. The mixture was stirred at room temperature for 18 h. After concentration in vacuo 0.5 N HCl (50 ml) was added and the mixture was extracted with dichloromethane (three times 50 ml). The combined organic layers were extracted with 0.5 N aqueous NaHCO3 solution, dried (MgSO4) and evaporated on the rotary evaporator. The residue was purified by flash chromatography (hexane/ethyl acetate=3:1) to yield 4.29 g (79%) of the tide compound as white crystalline solid.
Workup
- concentrationAfter concentration in vacuo 0.5 N HCl (50 ml)
- additionwas added
- extractionthe mixture was extracted with dichloromethane (three times 50 ml)
- extractionThe combined organic layers were extracted with 0.5 N aqueous NaHCO3 solution
- dry with materialdried (MgSO4)
- customevaporated on the rotary evaporator
- customThe residue was purified by flash chromatography (hexane/ethyl acetate=3:1)
Sources & evidence
- ORD record
- ord-a08a6cc83c7f44109e7146393ab1855b
- Source dataset
- uspto-grants-2008_05
- Patent number
- US07375099B2
Reaction notes
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