Cesium carbonate → HCID 118452436, compound

HRID 1773221Notes

Reaction equation

HRID 1773221 reaction equation
FC1C(C)=CC(O)=C(C=1)C=O.C([O-])([O-])=O.[Cs+].[Cs+].BrCC#N.[F:22][C:23]1[C:32]([CH3:33])=[CH:31][C:26]([O:27][CH2:28][C:29]#[N:30])=[C:25]([CH:34]=O)[CH:24]=1>C(#N)C>[F:22][C:23]1[C:32]([CH3:33])=[CH:31][C:26]2[O:27][C:28]([C:29]#[N:30])=[CH:34][C:25]=2[CH:24]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 11534BromoacetonitrileHCID 840703285-Fluoro-2-hydroxy-4-methylbenzaldehydeHCID 118452653HCID 118452653, compound

Product 1

HCID 118452436HCID 118452436, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To the solution of 5-fluoro-2-hydroxy-4-methylbenzaldehyde (500 mg, 3.24 mmol) in 10.5 ml acetonitrile in a microwave vial was added Cs2CO3 (1.268 g, 3.885 mmol), followed by 2-bromoacetonitrile (271 ul, 3.885 mmol). The reaction mixture was stirred at room temperature for 1 hr. LC/MS showed that all the starting material was converted to ring opened intermediate, 2-(4-fluoro-2-formyl-5-methylphenoxy)acetonitrile. LCMS retention time=1.19 minutes (R×NMON-Acidic:ZQ12); MS (m+1)=194.1. Then, the reaction vial was sealed, and the mixture was heated to 150° C. on microwave for 20 min. This reaction was repeated 20 times. The combined reaction mixture was filtered, washed with acetonitrile, the filtrate was concentrated. The residue was purified by silica gel flash chromatography (100% heptane-10% ethyl acetate/heptane) to give 5-fluoro-6-methylbenzofuran-2-carbonitrile (5.55 g). 1H NMR (400 MHz, DMSO-d6) δ 2.38 (d, J=2.2 Hz, 3H), 7.62 (d, J=9.3 Hz, 1H), 7.72 (d, J=6.0 Hz, 1H), 8.04 (d, J=1.0 Hz, 1H).

Workup

  1. customThen, the reaction vial was sealed
  2. temperaturethe mixture was heated to 150° C. on microwave for 20 min
  3. customThe combined reaction mixture
  4. filtrationwas filtered
  5. washwashed with acetonitrile
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by silica gel flash chromatography (100% heptane-10% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-7ea01657bab84c72bf98e2e913ef727b
Source dataset
uspto-grants-2016_02
Patent number
US09255093B2

Reaction notes

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