Dimethylformamide → HCID 22996207, compound

HRID 1167305Notes

Reaction equation

HRID 1167305 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[O:10][CH2:9][CH2:8][CH2:7]2.BrC1C=CC=C(Br)C=1O.[CH3:21][N:22](C)C=O>C(OCC)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[C:21]#[N:22])[CH2:7][CH2:8][CH2:9]1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 118472,6-DibromophenolHCID 225719898-Bromo-3,4-dihydro-2H-1-benzopyran

Product 1

HCID 22996207HCID 22996207, compoundYield 35%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 8-bromo-chroman (1.434 g, 6.730 mmol, prepared from 2,6-dibromo-phenol using the procedure reported by Thomas, G. H. et al. Tetrahedron Lett. 1998, 39, 2219-22) in dimethylformamide (10 mL) at room temperature was added zinc cyanide (790 mg, 6.730 mmol). The mixture was degassed by passing argon through for 2 h before tetrakis(triphenylphosphine)palladium (778 mg, 0.673 mmol) was added. The reaction mixture was heated at 90° C. for 12 h. Upon cooling to room temperature, it was diluted with diethyl ether (100 mL) and washed with sodium bicarbonate, brine and dried over anhydrous sodium sulfate. The solid was filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 10-20% ethyl acetate in hexanes yielded chroman-8-carbonitrile (370 mg, 35%).

Workup

  1. customThe mixture was degassed
  2. customthrough for 2 h
  3. additionwas added
  4. temperatureUpon cooling to room temperature
  5. washwashed with sodium bicarbonate, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe solid was filtered off
  8. concentrationthe filtrate was concentrated in vacuo
  9. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  10. washeluting with 10-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-10e9531151fa4d23a95e1370eaf6a0b4
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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