Dimethylformamide → 5-(Hydroxymethyl)-2-methoxybenzonitrile

HRID 1167320Notes

Reaction equation

HRID 1167320 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:10][OH:11])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH3:12][N:13](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>[OH:11][CH2:10][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([CH:3]=1)[C:12]#[N:13]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 13551346(3-Bromo-4-methoxyphenyl)methanol

Product 1

HCID 229961945-(Hydroxymethyl)-2-methoxybenzonitrileYield 51%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

To a solution of (3-bromo-4-methoxy-phenyl)-methanol (1 g, 4.607 mmol) in dimethylformamide (10 mL) at room temperature was added zinc cyanide (324.5 mg, 2.764 mmol). The reaction mixture was degassed by passing argon through for 30 min before tetrakis(triphenylphosphine)palladium (319 mg, 0.276 mmol) was added. The reaction mixture was heated at 80° C. for 12 h and stirred at room temperature for 2 d. It was diluted with diethyl ether (50 mL) and washed with sodium bicarbonate solution, brine and dried over anhydrous sodium sulfate. The solid was then 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 40% ethyl acetate in hexanes yielded 5-hydroxymethyl-2-methoxy-benzonitrile (385 mg, 51%) as a white solid.

Workup

  1. customThe reaction mixture was degassed
  2. customthrough for 30 min
  3. additionwas added
  4. washwashed with sodium bicarbonate solution, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe solid was then filtered off
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  9. washeluting with 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c0f4c344bb444f4fa05127ab1ac32e95
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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