Dimethylformamide → HCID 68431573, compound
Reaction equation
[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].F[C:19]1[C:26]([F:27])=[CH:25][C:22](C#N)=[C:21]([O:28][CH3:29])[CH:20]=1.CCOC(C)=O.[CH3:36][N:37](C=O)C>>[C:36]([C:19]1[C:26]([F:27])=[CH:25][C:22]([CH:4]([C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[C:21]([O:28][CH3:29])[CH:20]=1)#[N:37]Participants
Conditions
- Temperature
- 0 °C
Procedure
A suspension of NaH (60% in mineral oil, 0.33 g, 8.3 mmol) in dry DMF (20 mL) was stirred and cooled to 0° C., and di-tert-butyl malonate (1.5 g, 7.1 mmol) was added. The mixture was allowed to warm to room temperature before addition of 4,5-difluoro-2-methoxybenzonitrile (1.0 g, 5.9 mmol). The mixture was heated at 80° C. for 4 h with stirring, then the reaction mixture was cooled to room temperature and poured into a mixture of ice-water (100 mL) and AcOEt (100 mL). The layers were separated, and the organic layer was washed successively with water, and brine, then dried over Na2SO4 and concentrated. The residue was purified by flash chromatography (silica gel, EtOAc/hexanes, 0->10%) to give the di-tert-butyl (4-cyano-5-fluoro-2-methoxyphenyl)propanedioate. LCMS: [(M+1)−t-Bu, CO2−t-Bu]+=210.1; tR=2.2 min.
Workup
- temperatureThe mixture was heated at 80° C. for 4 h
- stirringwith stirring
- temperaturethe reaction mixture was cooled to room temperature
- customThe layers were separated
- washthe organic layer was washed successively with water, and brine
- dry with materialdried over Na2SO4
- concentrationconcentrated
- customThe residue was purified by flash chromatography (silica gel, EtOAc/hexanes, 0->10%)
Sources & evidence
- ORD record
- ord-b4f4e238f0114f38996168daaedc8789
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09018211B2
Reaction notes
Loading…