4-(Methylthio)benzyl bromide → Ammonium Hydroxide

HRID 392286

Reaction equation

HRID 392286 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9][CH3:10])=[CH:5][CH:4]=1.Cl[C:12]1[CH:21]=[N:20][CH:19]=[CH:18][C:13]=1[C:14]([O:16][CH3:17])=[O:15]>C1COCC1.[Zn].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Cl-].[Ni+2]>[NH4+:20].[OH-:15].[CH3:10][S:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][C:12]2[CH:21]=[N:20][CH:19]=[CH:18][C:13]=2[C:14]([O:16][CH3:17])=[O:15])=[CH:4][CH:5]=1

Participants

7

Reactant 2

HCID 113679304-(Methylthio)benzyl bromideHCID 15324397Methyl 3-chloroisonicotinate

Product 2

HCID 14923Ammonium HydroxideHCID 22663930Methyl 3-{[4-(methylsulfanyl)phenyl]methyl}pyridine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 84306Bis(triphenylphosphine)nickel(II)chlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 1-(bromomethyl)-4-(methylsulfanyl)benzene (prepared according to D. D. M. Wayner, D. R. Arnold, Can J. Chem., 1984, 62, 1164) (2.54 g, 11.7 mmol) in THF (10 mL) was added dropwise to a slurry of Riecke® Zinc in THF (22.8 mL of a commercial suspension [5 g Zn/100 mL], 17.5 mmol) under nitrogen. During this time the temperature rose steadily to 35° C. After allowing the black slurry to cool to room temperature over 30 min bis(triphenylphosphine)nickel (II) chloride (762 mg, 1.17 mmol) was added followed by a solution of methyl 3-chloroisonicotinate (prepared according to J. Epsztajn, M. W. Plotka, A. Grabowska, Synth. Commun., 1997, 27, 1075) (1.0 g, 5.83 mmol) in THF (10 mL), dropwise, taking care to keep the temperature below 30° C. After the addition was complete the reaction was allowed to cool to room temperature over 1 h before being quenched by the addition of sat. NH4Cl (aq) (20 mL) while cooling with an ice bath. The mixture was filtered through Celite®, washing well with EtOAc (3×20 mL), the organic layer was separated, dried (MgSO4) and evaporated to give a brown oil. The residue was purified by column chromatography [SiO2; EtOAc:pentane, 1:3 increasing polarity to EtOAc:pentane, 1:1 and then to (EtOAc:MeOH:NH4OH, 95:5:0.5):pentane, 1:1] to give the title compound as an orange oil; δH (CDCl3, 400 MHz) 2.43 (3H, s), 3.82 (3H, s), 4.30 (2H, s), 7.05 (2H, d), 7.18 (2H, d), 7.67 (1H, br), 8.59 (2H, br); MS m/z (TS+) 274 (MH+).

Workup

  1. customrose steadily to 35° C
  2. additionwas added
  3. customprepared
  4. customthe temperature below 30° C
  5. additionAfter the addition
  6. custombefore being quenched by the addition of sat. NH4Cl (aq) (20 mL)
  7. temperaturewhile cooling with an ice bath
  8. filtrationThe mixture was filtered through Celite®
  9. washwashing well with EtOAc (3×20 mL)
  10. customthe organic layer was separated
  11. dry with materialdried (MgSO4)
  12. customevaporated
  13. customto give a brown oil
  14. customThe residue was purified by column chromatography [SiO2

Sources & evidence

ORD record
ord-42f5b643e54b4c42bdc434d4c4460723
Source dataset
uspto-grants-2004_10
Patent number
US06800652B2

Linked notes

Loading…