Monoethyl malonate → Tert-butyl 4-(3-ethoxy-3-oxopropanoyl)piperazine-1-carboxylate

HRID 1665610Notes

Reaction equation

C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH2:20]([O:22][C:23](=[O:28])[CH2:24][C:25]([OH:27])=O)[CH3:21].CCN=C=NCCCN(C)C.Cl.[C:41]([O:45][C:46]([N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)=[O:47])([CH3:44])([CH3:43])[CH3:42]>CN(C=O)C.O>[C:41]([O:45][C:46]([N:48]1[CH2:53][CH2:52][N:51]([C:25](=[O:27])[CH2:24][C:23]([O:22][CH2:20][CH3:21])=[O:28])[CH2:50][CH2:49]1)=[O:47])([CH3:44])([CH3:42])[CH3:43]

Participants

Conditions

Temperature: 10 °C

Procedure

HOBt (3.48 g, 25.8 mmol) and DIPEA (6.94 g, 53.8 mmol) were added to a stirred solution of malonic acid monoethyl ester (2.84 g, 21.5 mmol) in DMF (10 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (4.95 g, 25.8 mmol) followed by piperazine-1-carboxylic acid tert-butyl ester (4 g, 21.5 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water. The product was extracted with ethyl acetate and the ethyl acetate was washed with brine solution, dried over Na2SO4 and concentrated to afford 5.2 g (84%) of 4-(2-ethoxycarbonyl-acetyl)-piperazine-1-carboxylic acid tert-butyl ester. LCMS: 301.17 (M+1)+ 84.5%. 1H NMR: (CDCl3): δ 4.0 (q, 2H), 3.45 (m, 2H), 3.3 (m, 8H), 1.25 (s, 9H), 1.1 (t, 3H).

Workup

additionwere added
extractionThe product was extracted with ethyl acetate
washthe ethyl acetate was washed with brine solution
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-5cad2fd7a5b442e0a19f77847023217d
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039463B2

Reaction notes

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