Formaldehyde → Diethyl acetamido[(piperidin-1-yl)methyl]propanedioate

HRID 1923991Notes

Reaction equation

[C:1]([NH:4][CH:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.[CH2:22]=O>C1COCC1>[C:1]([NH:4][C:5]([CH2:22][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of diethyl acetamidomalonate XC (1.75 g, 8.05 mmol) in THF (20 mL) was added piperidine (0.62 mL, 6.7 mmol) and 36% aqueous solution formaldehyde (0.23 mL, 8.25 mmol). The reaction mixture was stirred at 60° C. for 5 min. The mixture was cooled to −5° C. and kept at this temperature overnight. The precipitate was filtered to produce 1,3-diethyl 2-acetamido-2-(piperidin-1-ylmethyl)propanedioate XCI as a white crystallized solid (1.01 g, 3.21 mmol, 40% yield). 1H NMR (CDCl3) 1.15-1.30 (m, 6H), 1.31-1.56 (m, 6H), 2.03 (s, 3H), 2.30-2.51 (m, 4H), 3.25 (s, 2H), 4.13-4.32 (m, 4H), 6.99 (brs, 1H); ESIMS found for C15H26N2O5 m/z 315 (M+H).

Workup

temperatureThe mixture was cooled to −5° C.
customkept at this temperature overnight
filtrationThe precipitate was filtered

Sources & evidence

ORD record: ord-c9cdec201ebc4550827d6354e806171b
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178490B2

Reaction notes

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