N,N,N',N'-Tetramethylethylenediamine → HCID 90087871, compound

HRID 595033Notes

Reaction equation

[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12].CN(CCN(C)C)C.[Li]CCCC.CON(C)[C:32](=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[NH4+].[Cl-]>C(OC)(C)(C)C>[C:32]([C:4]1[C:3]([NH:9][C:10](=[O:15])[C:11]([CH3:12])([CH3:14])[CH3:13])=[C:2]([Cl:1])[C:7]([Cl:8])=[CH:6][CH:5]=1)(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

Conditions

Temperature: -23 °C

Procedure

To a cool (−23° C.), stirred solution of N-(2,3-dichlorophenyl)pivalamide (Shimada, I. et al., Bioorganic & Medicinal Chemistry, 16:1966-1982 (2008)), compound #12; 2.10 g, 8.53 mmol) and TMEDA (1.0 ml, 6.63 mmol) in t-BuOMe (21 ml) under N2 was added n-BuLi (7.9 ml, 19.75 mmol, 2.5M in pentane) via syringe over 15 min. The reaction mixture was stirred for 90 min. To the cool reaction mixture was added a solution of N-methoxy-N-methylbenzamide (2.46 g, 14.89 mmol) in t-BuOMe (11 ml) via cannula over 30 min, then the reaction mixture was allowed to warm to room temperature as the bath warmed. To the reaction mixture was added saturated NH4Cl, then the precipitated solid was collected by filtration, washed with water, and air dried overnight to afford Intermediate A25A (2.75 g, 88%) as a pale yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.04 (1H, br. s.), 7.76-7.83 (2H, m), 7.54-7.62 (1H, m), 7.43-7.49 (2H, m), 7.41 (1H, d, J=7.7 Hz), 7.35 (1H, d, J=7.7 Hz), 1.14 (9H, s).

Workup

customTo the cool reaction mixture
temperatureto warm to room temperature as the bath
temperaturewarmed
filtrationthe precipitated solid was collected by filtration
washwashed with water, and air
customdried overnight
customto afford Intermediate A25A (2.75 g, 88%) as a pale yellow solid

Sources & evidence

ORD record: ord-d683e50616d542c4815e69176ea9ceb9
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242941B2

Reaction notes

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