Benzyl Alcohol → 4-(Benzyloxy)-2-bromonicotinonitrile
Reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Br:11][C:12]1[N:19]=[CH:18][CH:17]=[C:16](Br)[C:13]=1[C:14]#[N:15]>CN(C=O)C>[CH2:3]([O:10][C:16]1[C:13]([C:14]#[N:15])=[C:12]([Br:11])[N:19]=[CH:18][CH:17]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a suspension of NaH (1.756 g, 45.818 mmol, mineral oil 60%) in DMF (200 ml) cooled at 0° C., was added benzyl alcohol (4.542 g, 42 mmol). The resulting mixture was stirred for 5 min. Then compound D1 (10 g, 38.18 mmol) was quickly added. The resulting reaction mixture was gradually warmed to r.t. and stirred for 1 h. The reaction mixture was quenched with NH4Cl (aqueous sat. solution), diluted with H2O and the resulting mixture was extracted with Et2O. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 1% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D2 (9.2 g, 83%).
Workup
- customThe resulting reaction mixture
- temperaturewas gradually warmed to r.t.
- stirringstirred for 1 h
- customThe reaction mixture was quenched with NH4Cl (aqueous sat. solution)
- additiondiluted with H2O
- extractionthe resulting mixture was extracted with Et2O
- customThe organic layer was separated
- dry with materialdried (Na2SO4)
- concentrationconcentrated in vacuo
- customThe crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 1% as eluent)
- customThe desired fractions were collected
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-4f4c651eabe443739a1fe8a9c18cf9af
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08937060B2
Reaction notes
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