Dimethylformamide → HCID 68431573, compound

HRID 1186983Notes

Reaction equation

HRID 1186983 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:14]([O:13][C:3](=[O:12])[CH:4]([C:22]1[CH:25]=[C:26]([F:27])[C:19]([C:36]#[N:37])=[CH:20][C:21]=1[O:28][CH3:29])[C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 120408344,5-Difluoro-2-methoxybenzonitrile

Product 1

HCID 68431573HCID 68431573, compound

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

  1. temperatureThe mixture was heated at 80° C. for 4 h
  2. stirringwith stirring
  3. temperaturethe reaction mixture was cooled to room temperature
  4. customThe layers were separated
  5. washthe organic layer was washed successively with water, and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (silica gel, EtOAc/hexanes, 0→10%)

Sources & evidence

ORD record
ord-4330fee4540f46d69021a31ec35d0b41
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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