N,N-DIBENZYLGLYCINE ETHYL ESTER

White to almost white crystalline powder

General procedure: A solution of amine (0.3 mmol in 4.0 mL EtGeneral procedure: A definite amount of polymer-supported ruthenium(II)-pheox complex cat. A was evacuated and backfilled with argon. The reaction flask was charged with (0.3 mmol) of amines dissolved in CH2Cl2 (3 mL) by injection through the side arm of the flask and the reaction flask was cooled in ice bath. Ethyldiazoacetate (0.035mL, 0.33 mmol) was slowly inserted and the reaction was stirred for 15 min at room temperature. The reaction product was isolated by centrifugation and the catalyst was separated by washing with acetonitrile and hexane respectively and dried under vacuum to be ready for the next use. The product in the filtrate was concentrated to afford the desired product in a pure form without further purification.General procedure: To a mixture of amine (2 mmol) and ethyl diazoacetate (see Table 1 for equivalents), [Hmim][BF4] (10 mol percent) was added. The mixture was stirred at room temperature until the completion of the reaction, as indicated by TLC. Next, H2O and CH2Cl2 were added. The mixture was decanted, the products being soluble in CH2Cl2. The ionic liquid being soluble in H2O was isolated after drying under vacuum and was reused in subsequent reactions.Dibenzylamine (VI-1) (4.7 g, 23.9 mmol) was dissolved in dichloromethane (10 ml), ethyl bromoacetate (V-1) (2.0 g, 12 mmol) was added with stirring at 25 ° C, a white solid precipitates. Continue to stir about 16h, TLC monitoring reaction is completed, filtered, the filter cake was washed with dichloromethane, the filtrate was concentrated under reduced pressure to give a crude solid, recrystallization from petroleum ether / ethyl acetate (100: 1) gave 3.3 g of a white solid, yield 97.3percent.Exam le 9To a solution of dibenzylamine 63 (13.8 mL, 71 .9 mmol, 1 .1 equiv) in absolute ethanol (50 mL), ethyl bromoacetate (7.25 mL, 65.4 mmol) is added. The reaction mixture is refluxed for 12 h under argon. After evaporation under vaccum of most of the ethanol, 1 N sodium hydroxide (100 mL) and dichloromethane (700 mL) are added, and the phases separated. The organic layer is washed with water (100 mL), brine (100 mL) and dried (anhydrous NaTo a stirred solution of ethyl chloroacetate (1.0 g, 8.16 mmol) in EtOH (5.0 mL), dibenzylamine (2.09 g, 10.6 mmol) was added and the mixture heated at 140 °C in a microwave reactor for 20 min. After evaporation of the solvent, the crude was dissolved in CC1Step 1. Glycine ethyl ester (10.3 g, 0.1 mol) was dissolved in dichloromethane (50 ml)Triethylamine (20.2 g, 0.2 mol) was added at 25 ° C, Benzyl chloride (25.32 g, 0.2 mol) was added with stirring, A white solid precipitates.Continue to stir, TLC monitoring reaction is completed, filter, The filter cake was washed with dichloromethane (20 ml)The combined filtrates were washed with water (100 ml)The organic layer was dried over anhydrous sodium sulfate, filter, Concentrated to give a solid, Recrystallization from petroleum ether / ethyl acetate (100: 1) gave 27.21 g of a white solid, The yield was 96.03percent.Under an atmosphere of nitrogen, 2- (dibenzylamino) acetate (IV-1) (2.0 g, 7.0 mmol) was dissolved in tetrahydrofuran (10 ml)Tetraisopropyl titanate (0.5 g, 1.7 mmol) was added, A solution of 1M ethylmagnesium bromide in tetrahydrofuran (21 ml, 21.0 mmol) was added at 10 C, Plus, Continue stirring.TLC monitoring reaction end, Saturated ammonium chloride solution quenched, Solid precipitation.filter, The filter cake was washed with ethyl acetate (50 ml x 2)The combined organic layers were washed with saturated sodium bicarbonate solution (50 ml)The organic layer was dried over anhydrous sodium sulfate, filter, Concentrated crude, Purification by flash column chromatography (petroleum ether: ethyl acetate = 5: 1)Get the oil, A total of 1.59g, The yield was 84.3%.Step 2: Preparation of 1-((diphenylmethylamino)methyl)cyclopropan-1-ol Titanium isopropoxide (622 mg, 2.33 mmol) was added to a solution of ethyl N-(phenylmethylene)glycinate (3.0 g, 11 mmol) in diethyl ether (100 mL) at room temperature. Ethylmagnesium bromide (3.0 M Et2O solution, 10.6 mL, 31.8 mmol) was added dropwise and slowly, and the mixture was stirred for 12 hours at room temperature. After the reaction was cooled to 0C, hydrochloric acid (2M, 10mL) was added slowly, then the reaction was warmed up to room temperature slowly and stirred for 30 minutes. After addition of saturated NaHCO3 aqueous solution (60 mL), the reaction solution was stirred for 10 minutes, extracted twice with CH2Cl2, and concentrated. The resulting residue was subjected to column chromatography to obtain the title compound 1-((diphenylmethylamino)methyl)cyclopropan-1-ol (1.7 g, 60%). MS m/z (ESI): 268.2 [M+H]+.Under a nitrogen atmosphere, a 3.0 M solution of ethylmagnesium bromide in THF (9.41 mL) was added dropwise to a solution of (A) 1-((Dibenzylamino)methyl)cyclopropanol To a mixture of To a stirred solution of ethyl chloroacetate (1.0 g, 8.16 mmol) in EtOH (5.0 mL), dibenzylamine (2.09 g, 10.6 mmol) was added and the mixture heated at 140 C in a microwave reactor for 20 min. After evaporation of the solvent, the crude was dissolved in CC12 and washed with a l.O M KOH solution and brine, then dried over Na2S04, filtered, and concentrated in vacuo to give a crude product, as an oil. Purification by column chromatography using a Teledyne ISCO apparatus, eluting with Cy:EtOAc (98:2), gave the title compound (1.85 g, 80%), as a white solid. MS (ESI) m/z: 284 [M-H]+ [1HNMR as previously reported in literature: Synthesis, 1985, 9, 850-855].Step 1. Preparation of

Molecular Weight:283.4
XLogP3:3.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:8
Exact Mass:283.157228913
Monoisotopic Mass:283.157228913
Topological Polar Surface Area:29.5
Heavy Atom Count:21
Complexity:274
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes