Sodium hydride → HCID 64905840, compound
Reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]#[N:12])=[CH:6][CH:5]=1.Br[CH2:14][C:15]([O:20][CH3:21])([O:18][CH3:19])[CH2:16]Br>CN(C=O)C>[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:11]#[N:12])[CH2:16][C:15]([O:20][CH3:21])([O:18][CH3:19])[CH2:14]2)=[CH:6][CH:5]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
To a solution of NaH (1.302 g, 32.6 mmol, 60 wt % in mineral oil) in dry DMF (10 mL) cooled to 0° C., was added dropwise a solution 2-(4-fluorophenyl)acetonitrile (2.0 g, 14.8 mmol) in DMF (10 mL) To the stirred suspension at 0° C. was then added 1,3-dibromo-2,2-dimethoxypropane (3.88 g, 14.80 mmol). The reaction mixture was then heated to 60° C. and stirred for 12 h. The reaction mixture was cooled to RT, quenched with water and extracted with EtOAc (3×20 mL). The combined organic layers were washed with water and brine, dried over Na2SO4 and evaporated. The crude compound was purified by silica gel chromatography (24 g REDISEP® column, eluting with 20% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 308A as a yellow liquid (1.4 g, 40%). 1H NMR (400 MHz, chloroform-d) δ ppm 7.45 (dd, J=8.94, 5.05 Hz, 2H), 7.09 (t, J=8.66 Hz, 2H), 3.28 (s, 3H), 3.05-3.19 (m, 5H), 2.64-2.72 (m, 2H).
Workup
- temperatureThe reaction mixture was cooled to RT
- customquenched with water
- extractionextracted with EtOAc (3×20 mL)
- washThe combined organic layers were washed with water and brine
- dry with materialdried over Na2SO4
- customevaporated
- customThe crude compound was purified by silica gel chromatography (24 g REDISEP® column, eluting with 20% EtOAc in hexanes)
- additionFractions containing the product
- customevaporated
Sources & evidence
- ORD record
- ord-b63983ce617c4a28aefb39eef3765b21
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273058B2
Reaction notes
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