1-(1H-Imidazol-1-yl)ethanone → tert-Butyl 3-acetyl-4-oxopiperidine-1-carboxylate

HRID 712447Notes

Reaction equation

[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Li+].CC([N-]C(C)C)C.[C:23](N1C=CN=C1)(=[O:25])[CH3:24]>C1COCC1>[C:23]([CH:7]1[C:2](=[O:1])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6]1)(=[O:25])[CH3:24]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (6.00 g) in THF was added LDA (16 mL, 1 M) dropwise at −78° C. The mixture was stirred at −78° C. for 2 h. To this, a solution of N-acetylimidazole (3.50 g) in THF was added, and the reaction mixture was stirred at −78° C. for another 7 h, then quenched with 10 mL of ice-water and extracted with CH2Cl2 (50 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA) to give the title compound as yellow oil (2.98 g, 41.00%), HPLC: 89.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 242.4 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 2.13 (s, 3H), 2.28 (s, 1H), 2.44 (t, J=4.0 Hz, 2H), 3.58 (t, J=8.0 Hz, 2H), 3.97 (s, 2H) ppm.

Workup

stirringthe reaction mixture was stirred at −78° C. for another 7 h
customquenched with 10 mL of ice-water
extractionextracted with CH2Cl2 (50 mL×3)
dry with materialThe combined organic phases were dried over anhydrous Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo
customthe residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA)

Sources & evidence

ORD record: ord-c65d60d6f5b74d58924866682420e07f
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181277B2

Reaction notes

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