Dimethylformamide → 3-(Hydroxymethyl)-5-methoxybenzonitrile

HRID 1167334Notes

Reaction equation

HRID 1167334 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:10][OH:11])[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.[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:3]=[C:2]([CH:7]=[C:6]([O:8][CH3:9])[CH:5]=1)[C:12]#[N:13]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 10608788(3-Bromo-5-methoxyphenyl)methanol

Product 1

HCID 229962263-(Hydroxymethyl)-5-methoxybenzonitrileYield 78%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of 3-bromo-5-methoxy-phenyl-methanol (460 mg, 2.119 mmol, prepared according to the procedure reported by Claudi, F. et al. J. Med. Chem. 2000, 43, 599-608) in dimethylformamide (3 mL) at room temperature was added zinc cyanide (149 mg, 1.271 mmol). The reaction mixture was degassed by passing argon through for 30 min before tetrakis(triphenylphosphine)palladium (147 mg, 0.127 mmol) was added. The reaction mixture was heated at 100° C. for 12 h. It was diluted with diethyl ether 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 3-hydroxymethyl-5-methoxy-benzonitrile as white solids (269 mg, 78%).

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-a096b5d5f7424ee58ddb972d80483367
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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