Sodium hydride → HCID 68669299, compound

HRID 1161951Notes

Reaction equation

[CH2:1]([N:5]1[CH2:10][CH2:9][NH:8][C:7](=[O:11])[C:6]1=[O:12])[CH2:2][CH2:3][CH3:4].[H-].[Na+].Br[CH:16]([CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]([O:19][CH3:20])=[O:18]>CN(C=O)C>[CH2:1]([N:5]1[CH2:10][CH2:9][N:8]([CH:16]([CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:17]([O:19][CH3:20])=[O:18])[C:7](=[O:11])[C:6]1=[O:12])[CH2:2][CH2:3][CH3:4]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of 1-butylpiperazine-2,3-dione (Intermediate D, 500 mg, 2.9 mmol) in 4 mL DMF, cooled to 0° C., was added sodium hydride (60% dispersion in mineral oil, 128 mg, 3.2 mmol). The reaction was stirred at rt for 30 min, recooled to 0° C. and a solution of methyl 2-bromo-4-phenylbutanoate (Intermediate C, 820 mg, 3.2 mmol) in 1 mL DMF was added dropwise. The mixture was stirred at rt for 1 h, quenched with brine and extracted with EtOAc. Drying, solvent evaporation and flash chromatography (silica gel, 35-90% EtOAc/hexanes) gave methyl 2-(4-butyl-2,3-dioxopiperazin-1-yl)-4-phenylbutanoate. 1H NMR (CDCl3) δ 7.29 (m, 2H), 7.18 (m, 3H), 5.27 (X of ABX, 1H, J=10.8 Hz, J=4.6 Hz), 3.72 (s, 3H), 3.63 (m, 1H), 3.54 (m, 1H), 3.47 (m, 2H), 3.38 (m, 1H), 3.28 (m, 1H), 2.67 (m, 2H), 2.36 (m, 1H), 2.03 (m, 2H), 1.57 (m, 2H), 1.35 (m, 2H), 0.95 (t, 3H, J=7.3 Hz).

Workup

customrecooled to 0° C.
stirringThe mixture was stirred at rt for 1 h
customquenched with brine
extractionextracted with EtOAc
customDrying
customsolvent evaporation and flash chromatography (silica gel, 35-90% EtOAc/hexanes)

Sources & evidence

ORD record: ord-4b4e3d16b76446419f02ca9b02feba53
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820674B2

Reaction notes

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