1-Boc-3-oxopiperazine

White to off-white solid

To a mixture of piperazine-2-one (1.037 g, 10.4 mmol) in 52 mL of CH2Cl2, was added BOC20 (2.5 g, 11.4 mmol). The reaction became homogeneous after 3 hours when the starting material was completely consumed. The reaction was diluted with CH2Cl2 and the organic layer was washed with water. The solvent was removed in vacuo to yield quantitative amount of product 33 as a white solid. Di-tert-butyl dicarbonate (3.92 g, 17.98 mmol) was added to a suspension of 2-piperazinone (1.50 g, 14.98 mmol) in dichloromethane (15 mL). The mixture was stirred at room temperature for 5 hours. The solvent was evaporated to afford 1 , 1- dimethylethyl 3-oxo-1-piperazinecarboxylate (2.99 g, quantitative) as an off-white solid.BocPreparation Example 1-25-13-Oxo-piperazine-1-carboxylic acid tert-butyl ester piperazin-2-one (500 mg, 5.0 mmol) was dissolved in methanol (15 mL), and di t-butyl dicarbonate (1.09 g, 5.0 mmol) was added thereto and the mixture was stirred for 16 hours. The mixture was distilled under reduced pressure to remove the solvent, and purified by column chromatography using 5:95 mixture solvent of methanol and dichloromethane to obtain the title compound (0.99 g, 99percent).1) STEP 1 Piperazin-2-one (1 g, 10 mmol) was dissolved in CH2C12 (40 ML), and BOC20 (2.4 g, 11 mmol, 1.1 eq), Et3N (2.02 g, 20 mmol, 2 eq) and DMAP (0.024 g, 0.2 mmol, 2 molpercent) were added. After the mixture was stirred at RT for 16 h, it was acidified with 1 N HCI. The organic layer was separated, washed with saturated NAHC03, brine, dried (Na2SO4), and concentrated in vacuo to give the product (1.8 g, 90percent) as a white SOLID. H NMR (CDCI3, 300 MHz) No. 6. 70 (1 H, bs), 4.08 (2H, s), 3.62 (2H, t, J = 6. 0 Hz), 3.37 (2H, m), 1.46 (9H, s).To a solution of piperazinone (10.0 g, 100 mmol), triethylamine (20.2 g, 200mmol), and DMAP (50 mg) in CHTo a solution of piperazinone (10.0 g, 100 mmol), Triethylamine (20.2 g, 200mmol), and DMAP (50 mg) in CHaCIa (250 ml) in an ice water bath was added(Boc)Step 1: Example 29 Step 1: Piperazin-2-one (1 g, 10 mmol) was dissolved in CH2CI2 (40 ML), and BOC20 (2.4 g, 11 MMOL, 1.1 eq), ET3N (2.02 g, 20 mmol, 2 eq) and DMAP (0.024 g, 0.2 mmol, 2 molpercent) were added. After the mixture was stirred at RT for 16 h, it was acidified with 1 N HCI. The organic layer was separated, washed with saturated NAHC03, brine, dried (NA2SO4), and concentrated in vacuo to give the product (1.8 g, 90percent) as a white solid.'H NMR (CDC13, 300 MHz) 8 6. 70 (1 H, bs), 4.08 (2H, s), 3.62 (2H, t, J = 6. 0 Hz), 3.37 (2H, m), 1.46 (9H, s).[Referential Example 90]; 4-Methyl-3-oxopiperazine-1-carboxylic acid tert-butyl ester; 1) 3-Oxopiperazine-1-carboxylic acid tert-butyl ester ; Triethylamine (3.9 mL) and di-tert-butyl dicarbonate (6.31 g) were added to 2-oxopiperazine (2.61 g) in a mixture of tetrahydrofuran (40 mL) and methanol (50 mL) at room temperature, followed by stirring for 3 hours. The solvent was evaporated under reduced pressure. To the residue, diethyl ether was added, and the precipitated solid was recovered by filtration, to thereby give 3-oxopiperazine-1-carboxylic acid tert-butyl ester (4.54 g, 87percent).1H-NMR(400MHz, DMSO-d6)δ: 1.40(9H, s), 3.15(2H, br), 3.45(2H, br), 3.81(2H, br), 8.03(1H, br). LC-MSm/z: 201(M+H)+.1) 1) 1) 3-Oxopiperazine-1-carboxylic acid tert-butyl ester Triethylamine (3.83 mL) and di-tert-butoxydicarbonate (6.32 mL) were added to a mixed solution of piperazin-2-one (2.5 g) in tetrahydrofuran (50 mL) and methanol (50 mL) at room temperature, and the resultant mixture was stirred for 4 hours. The reaction solvent was evaporated under reduced pressure, water and ethyl acetate were added to the residue thus obtained, and the mixture was partitioned. The organic layer was washed with water and saturated saline in this order, and then the washing water layer was combined for further extraction with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. After separation by filtration, a residue obtained by evaporating the solvent under reduced pressure was solidified using ethyl acetate-hexane, thus to obtain 3-oxopiperazine-1-carboxylic acid tert-butyl ester (3.6 g, 72percent). 1) 3-oxopiperazine-1-carboxylic acid tert-butyl ester Triethylamine (3.83 ml) and di-tert-butoxydicarbonate (6.32 ml) were added to a mixed solution of piperazin-2-one (2.5 g) in tetrahydrofuran (50 ml) and methanol (50 ml) at room temperature, and the resultant mixture was stirred for 4 hours. The reaction solvent was evaporated under reduced pressure, then water and ethyl acetate were added to the residue thus obtained, and the mixture was partitioned. The organic layer was washed sequentially with water and saturated brine, and then the washing water layers were combined and extracted again with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate. After separating the organic layer by filtration, the solvent was evaporated under reduced pressure, and a residue thus obtained was solidified from ethyl acetate-hexane, to obtain 3-oxopiperazine-1-carboxylic acid tert-butyl ester (3.6 g, 72percent). Piperazine -2-one( 2g, 20 mmol) is added to DCM (30 mL) , and under the protection of argon Et3N (3.46 mL, 24 mmol) is added , after cooling down the room temperature to 0 , add BOC anhydride (4.79g, 22mmol) in one reaction flask and raise the room temperature . After 3 h, reaction is stopped and DCM (100 mL) is added, washed with saturated NaCl solution (30 mL x 2), dried over anhydrous magnesium sulfate, concentrated, and recrystallized from DCM and petroleum ether to give a white solid 2.8 g, yield 70percent.To a solution of piperadine-2-one (2.01 g) in dioxane (20 mL) and water (10 mL), an aqueous solution of two normal sodium hydroxide (10 mL) was added at room temperature and stirred. Then, a solution of tert-butyl dicarbonate (5.45 g) in dioxane (5 mL) was slowly added dropwise, and stirred as it is at room temperature for eight hours. Water was poured to the reaction mixture, and extracted twice with 50 mL of ethyl acetate. After the organic layers were combined and washed in saturated saline, it was dried on anhydrous magnesium sulfate, and filtered. The solvent was evaporated under reduced pressure, dried under vacuum to obtain a title compound (3.41 g, yield 68percent) as a white solid compound. The product thus obtained was used in the subsequent reaction without further purification. ESI/MS m/e: 201.2 (M++H, C9H16N2O3)To a stirred solution of piperazin-2-one CK (3 g, 30 inmol) in CHjCfe (50 mL) under argon atmosphere were added tiiethylamine (8.65 mL. 60 mmol) and di-t-buryi dicarbonate (Boc anhydride, 8.2 mL, 36 niniol) at 0 °C. The reaction was wanned to RT and stirred for 16 h. The reaction was diluted with water (100 mL) and the product was extracted with CC (2 x 100 mL). The combined organic layers were dried over anhydrous Na S< and concentrated under reduced pressure to obtain Compound CO (4 g, 20 mmol, 66 percent) as a white solid, which was used in the next step without further purification. H NMR (400 MHz, CDCi3): δ 6.90 (br s. IH), 4.08 (s, 2H), 3.63-3.59 (m, 2H), 3.35-3.31 (m, 2H), 1.44 (s. 9H).To a stirring solution of piperazin-2-one 16 (500 mg, 5.00 mmol) in CH2-Piperazinone (2.5 g; 24.97 mmol) was dissolved in DCM ( 55 ml ). A solution of tert- butyloxycarbonyl anhydride (5.45g, 24.97mmol) in DCM (20 ml) was added dropwise. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated to dryness and dried under high vacuum, at room temperature. The residue containing Int. 177 (5.1 g) was used as such in the next reaction step.Intermediate 1: 4-(tert-Butyloxycarbonyl)piperazin-2-one

Molecular Weight:200.23
XLogP3:0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:200.11609238
Monoisotopic Mass:200.11609238
Topological Polar Surface Area:58.6
Heavy Atom Count:14
Complexity:245
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes