4-(1-Hydroxyethyl)benzonitrile → HCID 57878394, compound

HRID 2059735Notes

Reaction equation

HRID 2059735 reaction equation
[OH:1][CH:2]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1)[CH3:3].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([Mg]Br)=[CH:15][CH:14]=1>C1COCC1>[NH2:9][CH:8]([C:16]1[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][CH:15]=1)[C:7]1[CH:10]=[CH:11][C:4]([CH:2]([OH:1])[CH3:3])=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 5833354-(1-Hydroxyethyl)benzonitrileHCID 178478191HCID 178478191, compound2×

Product 1

HCID 57878394HCID 57878394, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The product of Step A (1.47 g, 10 mmol) was dissolved in THF (20 mL), cooled in an ice-bath and 4-chlorophenylmagnesium bromide (21.00 mL, 21.00 mmol, 1 M in THF) was added. The reaction aged at 50° C. for 4 h and then cooled to rt overnight. The solvent had evaporated overnight and the product was taken up in 2-methyltetrhydrofuran (20 mL) and an additional 1 eq of 4-chlorophenylmagnesium bromide was added. The reaction aged at rt for 3 h and was concentrated. The reaction was diluted with 15 mL MeOH. NaBH (378 mg, 10.00 mmol) was added and the reaction aged for 1 h. The reaction was concentrated, diluted with 2M HCl (aq) and extracted with EtOAc. The organic layer was collected, dried with Na2SO4, filtered and concentrated. The residue was purified somewhat by flash chromatography on silica gel gradient eluted with 0-10% MeOH/EtOAc affording title compound. HPLC/MS: 244.9 (M—NH2)+; Rt=2.09 min

Workup

  1. temperaturecooled in an ice-bath
  2. customThe solvent had evaporated overnight
  3. waitThe reaction aged at rt for 3 h
  4. concentrationwas concentrated
  5. additionThe reaction was diluted with 15 mL MeOH
  6. waitthe reaction aged for 1 h
  7. concentrationThe reaction was concentrated
  8. additiondiluted with 2M HCl (aq)
  9. extractionextracted with EtOAc
  10. customThe organic layer was collected
  11. dry with materialdried with Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified somewhat by flash chromatography on silica gel gradient
  15. washeluted with 0-10% MeOH/EtOAc affording title compound

Sources & evidence

ORD record
ord-2808e48a073b43b6b990364ad92007ee
Source dataset
uspto-grants-2012_10
Patent number
US08278304B2

Reaction notes

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