BENZYL 3-OXOPIPERAZINE-1-CARBOXYLATE

White solid

Step 2 General procedure: To a solution of 3-aminopyrrolidine-1-carboxylate (744 mg, 4 mmol) in DCM (10 mL) , DIEA(1.04 mL, 6 mmol) and benzyl chloroformate (0.72 mL, 5 mmol) were added at 0. The reactionmixture was stirred at room temperature until TLC monitoring showed that the reaction wascomplete. The mixture was diluted with DCM and washed with water and brine. The organic layerwas dried over anhydrous MgSO4andevaporated, and column chromatography (petroleum ether /ethyl acetate =8:1 to 5:1) to give the corresponding product I-4 as light yellow oil (1.05 g, 82percent).Piperazine-2-one (1 g, 10 mmol) is added to ethyl acetate (40 mL), In the solution of 20 ml , K2CO3 is added at the room temperature followed by Benzyloxycarbonyl chloride (2.1 mL, 15 mmol) is added dropwise to the reaction flask, and reaction is stirred at room temperature . The reaction stopped next day, and the organic layer is washed with 20 mL of X saturated NaCl solution, dried over anhydrous magnesium sulfate, Column chromatography (D: Μ = 75: 1) to obtain a white solid 1.48, 59.8percent.yield.C. 3-Oxo-4-prop-2-ynylpiperazine-1-carboxylic acid benzyl ester. sodium hydride (0.82 g, 23.0 mmol, 60% mineral oil dispersion) is added to a solution of A. 4-(4-Cyanobenzyl)-3-oxopiperazine-1-carboxylic acid benzyl ester. To a solution of 3-oxo-piperazine-1-carboxylic acid benzyl ester (3.0 g, 12.8 mmol) and 4-bromomethyl tolylnitrile (2.76 g, 14.1 mmol) in 135 ML of THF and 15 ML of DMF at 0 C. is added a 60% dispersion in mineral oil of NaH (0.49 g, 12.8 mmol).After 5 hours, the solution is diluted with saturated NH4Cl and EtOAc. The organic layer is washed with H2O and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated.The crude product is purified by column chromatography over silcia gel eluding with 20% EtOAc/CH2Cl2.The title compound is obtained as a white solid (4.01 g, 11.4 mmol).1H NMR (CDCl3, 300 MHz) delta7.62 (d, 2H), 7.39 (m, 7H), 5.14 (s, 2H), 4.68 (s, 2H), 4.27 (s, 2H), 3.73 (m, 2H), 3.30 (m, 2H).In a 5L four-necked flask, add 1.5L of N, N-dimethylformamide, And added 36.4g of sodium hydride, Mechanically stir, add 177 g of benzyl 3-oxopiperazine-1-carboxylate in batches, Stir at room temperature for 1 h.In an ice-water bath, 129.2 g of methyl iodide was slowly added dropwise to the reaction solution.It was naturally warmed to room temperature and reacted for 12 h.TLC analysis of the raw materials was complete, Extract the reaction solution with 500ml of distilled water, Concentrated off part of N, N-dimethylformamide, Add distilled water and extract six times with ethyl acetate (6 × 1L).Concentrated and dried, The 4-methyl-3-oxopiperazine-1-carboxylic acid benzyl ester was obtained as a solid, and the next step was directly carried out. The yield was 100%.General procedure: The appropriate nucleophile (1 equiv.), the epoxide (1-3 equiv.) and a base (1-5 equiv.) were suspended in a solvent and the reaction mixture was heated under the stated conditions. (0735) The reaction was allowed to cool to rt, saturated NH4CI(aq) or water was added and the resulting mixture was extracted using DCM or EtOAc (x 3). The combined organic extracts were dried (phase separator or MgS04), concentrated under reduced pressure and the remaining residue was purified by flash chromatography to give the product.

Molecular Weight:234.25
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:234.10044231
Monoisotopic Mass:234.10044231
Topological Polar Surface Area:58.6
Heavy Atom Count:17
Complexity:288
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes