Using alkylmetal reagents for directed metalation of azaaromatics
A technology of metal alkyls and compounds, which is applied in the metallization of compounds and the metallization of azaaromatic compounds, can solve the problems of low temperature, difficult formation process, and difficult availability of reactants, etc., to achieve improved production rate effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0031] Deprotonation of azaaromatic compounds using (trimethylsilylmethyl)lithium
[0032] A solution of (trimethylsilylmethyl)lithium (106 mL, 12.8 wt % in hexanes) was placed in a 250 mL three necked round bottom flask and cooled to -40 °C. A solution of 4-methoxypyridine (10.0 g) in tetrahydrofuran (THF) (111 mL) was added over one hour below -30°C. Lithiation is complete after about 1.5 hours. 1-Formylpiperidine (10.6 g) was added within 5 minutes at -35°C. After 1.5 hours the reaction mixture was quenched with acetic acid (15 mL) and water (35 mL). The aqueous layer was separated and rinsed with 4 x 25 mL EtOAc. Combine all organic layers and wash with MgSO 4 Drying and concentration in vacuo gave 16.0 g of a yellow oil which crystallized on cooling. After trituration with 30 mL hexane / 1 mL isopropanol, the material had a GC area % purity of 96.5% (13.02 g, 99% yield, corrected for experimentation). Recrystallization from IPA / hexane (1:3) gave the desired product in...
Embodiment 2
[0034] Deprotonation of azaaromatic compounds using (trimethylsilylmethyl)lithium
[0035] A solution of (trimethylsilylmethyl)lithium (22 mL, 13.8 wt % in hexane) was placed in a 100 mL three necked round bottom flask and cooled to -50 °C. A solution of 2-fluoropyridine (2.0 g), THF (25 mL) and diisopropylamine (0.13 mL) was added within 1 min below -50 °C. After 3 hours, 1-formylpiperidine (2.4 g) was added within 1 minute below -50°C. The mixture was warmed to room temperature and stirred overnight. The reaction mixture was quenched with acetic acid (3 mL) and water (7 mL). The aqueous layer was separated and rinsed with 3 x 25 mL MTBE. Combine all organic layers and wash with MgSO 4 Drying and concentration in vacuo gave 3.79 g of a brown oil. The oil was chromatographed on silica gel eluting with 15% EtOAc in hexanes to afford 2.24 g of 2-fluoro-3-pyridinecarbaldehyde in 92.4% purity (90% yield, corrected for assay).
Embodiment 3
[0037] Deprotonation of azaaromatic compounds using (trimethylsilylmethyl)lithium
[0038] A mixture of 2-methoxypyridine (23.2 g) and diisopropylamine (1.35 mL) in THF (223 mL) was added to (trimethylsilylmethyl)lithium (218 mL in hexanes) at -20 °C , 13.8% by weight). After 7 hours 84% lithiation was complete. Triisopropyl borate (40.8 g) was added over 40 minutes at -20°C. The mixture was stirred overnight at room temperature. 5% NaOH (aq, 225 mL) was added. The aqueous layer was removed and brought to pH 5 by adding 10% HCl(aq). The resulting white precipitate was isolated by filtration. After drying, 22.23 g of 2-methoxypyridine-3-boronic acid were obtained (68% yield).
PUM
Login to view more Abstract
Description
Claims
Application Information
Login to view more - R&D Engineer
- R&D Manager
- IP Professional
- Industry Leading Data Capabilities
- Powerful AI technology
- Patent DNA Extraction
Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.
© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap