Dimethyl Sulfate → 7-Methoxynaphthalen-2-amine

HRID 1710205Notes

Reaction equation

HRID 1710205 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([OH:12])=[CH:7][CH:8]=2)[CH:3]=1.[H-].[Na+].[H][H].S(OC)(O[CH3:21])(=O)=O>CN(C=O)C.CCCCCC>[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([O:12][CH3:21])=[CH:7][CH:8]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 667322-Amino-7-naphtholHCID 178418361HCID 178418361, compound

Product 1

HCID 148760287-Methoxynaphthalen-2-amine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

2-Amino-7-hydroxynaphthalene (18.6 g, 0.117 mol) was added in portions to hexane-rinsed NaH (60%, 5.1 g, 0.127 mol) in dry DMF (dimethylformamide; 100 ml) at 0° C. The solution was stirred under argon for 10 minutes until hydrogen evolution had ceased, whereupon dimethyl sulfate (11 ml, 0.116 mol) was added dropwise via syringe at 0° C. until O-methylation was complete by TLC monitoring. The reaction was carefully quenched with 6N HCl to pH 1, and partitioned between ether and water, thus separating the naphthylamine hydrochloride from organic impurities. After washing the ether layer with 6N HCl, the aqueous layers were combined, neutralized with NaOH pellets to pH 8 and partitioned with EtOAc to recover the free amine in the organic layer. The basic aqueous layer was washed twice with EtOAc, and the combined EtOAc layers were dried over Na2SO4 and evaporated. Upon removal of DMF under high vacuum, the product mixture crystallized. Crystals of 2-amino-7-methoxynaphthalene (19.4 g, 96.5%) were collected from MeOH, m.p. 157° C.

Workup

  1. customThe reaction was carefully quenched with 6N HCl to pH 1
  2. custompartitioned between ether and water
  3. customthus separating the naphthylamine hydrochloride from organic impurities
  4. washAfter washing the ether layer with 6N HCl
  5. custompartitioned with EtOAc
  6. customto recover the free amine in the organic layer
  7. washThe basic aqueous layer was washed twice with EtOAc
  8. dry with materialthe combined EtOAc layers were dried over Na2SO4
  9. customevaporated
  10. customUpon removal of DMF under high vacuum
  11. customthe product mixture crystallized
  12. customCrystals of 2-amino-7-methoxynaphthalene (19.4 g, 96.5%) were collected from MeOH, m.p. 157° C.

Sources & evidence

ORD record
ord-52aeba0a63184d39a578631254562beb
Source dataset
uspto-grants-1990_08
Patent number
US04952707

Reaction notes

Loading…