Potassium Carbonate → tert-butyl N-(5-cyano-2-fluorobenzyl)-N-methyl-beta-alaninate
Reaktionsgleichung
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:11])=[C:7]([CH:10]=1)[CH2:8]Br)#[N:2].[CH3:12][NH:13][CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C(=O)([O-])[O-].[K+].[K+]>CC#N>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:11])=[C:7]([CH:10]=1)[CH2:8][N:13]([CH3:12])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])#[N:2]Komponenten
Reaktionsbedingungen
- Temperatur
- 60 °C
Versuchsvorschrift
A mixture of 5-cyano-2-fluorobenzylbromide (CARBOCORE; CO-0137; 1.50 g; 7.01 mmol; 1 eq.), tert-butyl N-methyl-beta-alaninate (1.34 g; 8.41 mmol; 1.20 eq.) (prepared as described by Howard N., I. et al. in Bioorg. Med. Chem. 11 (2003), 3083-3099) and potassium carbonate (1.94 g; 14.02 mmol; 2 eq.) in CH3CN (25 mL) was stirred at 60° C. for 6 hours then at RT for 16 hours. The acetonitrile was evaporated in vacuo and the resulting mixture diluted with water. Extraction with EtOAc, washing with NaCl sat. solution, drying over sodium sulfate and concentration in vacuo gave title compound as a slightly yellow oil (1.9 g; 92%). 1H NMR (CDCl3) δ 7.79 (dd, J=6.7, 2.1 Hz, 1H), 7.57-7.52 (m, 1H), 7.11 (t, J=8.9 Hz, 1H), 3.57 (s, 2H), 2.74 (t, J=7.1 Hz, 2H), 2.43 (t, J=7.1 Hz, 2H), 2.22 (s, 3H), 1.45 (s, 9H). LC/MS (Method B): 293.2 (M+H)+. HPLC (Method A) Rt 2.44 min (Purity: 86.4%).
Aufarbeitung
- waitat RT for 16 hours
- customThe acetonitrile was evaporated in vacuo
- additionthe resulting mixture diluted with water
- extractionExtraction with EtOAc
- washwashing with NaCl sat. solution
- dry with materialdrying over sodium sulfate and concentration in vacuo
Quellen und Nachweise
- ORD-Eintrag
- ord-c8ca3a328c884567a1cdf62584df45a8
- Quelldatensatz
- uspto-grants-2012_06
- Patentnummer
- US08202865B2
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