Water → 4-(Methanesulfonylmethyl)-2-methoxyaniline

HRID 1014236Notes

Reaction equation

HRID 1014236 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[N+:11]([O-])=O)[CH2:6]Cl.[Na+].[CH3:15][S:16]([O-:18])=[O:17].O>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:6][S:16]([CH3:15])(=[O:18])=[O:17])[CH:8]=[CH:9][C:10]=1[NH2:11]

Participants

5

Reactant 3

HCID 962WaterHCID 2733271Sodium methanesulfinateHCID 220516194-(Chloromethyl)-2-methoxy-1-nitrobenzene

Product 1

HCID 594419624-(Methanesulfonylmethyl)-2-methoxyanilineYield 83.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-methoxy-4-nitrobenzyl chloride (2.76 g, 13.7 mmol) in 20 mL of absolute ethanol was added methanesulphinic acid sodium salt (1.0 g, 27.4 mmol). The reaction was heated to 80° C. for 16 h. The reaction was cooled to room temperature and poured into water and the aqueous layer was extracted with ethyl acetate. Combined organics were dried over anhydrous MgSO4, filtered, concentrated onto silica gel and purified by flash chromatography with ethyl acetate/hexanes as the eluent. The fractions containing the desired product were concentrated to dryness, then redisolved in absolute ethanol and 10% Palladium on carbon (500 mg) was added and the reaction was placed on the Fischer-Porter hydrogenation apparatus and treated with 50 psi of H2 gas overnight to afford 2-(methyloxy)-4-[(methylsulfonyl) methyl]aniline (2.46 g, 83%). 1H NMR (400 MHz, CDCl3) δ ppm 6.80 (d, J=1.7 Hz, 1H), 6.68 (d, J=8.0, 1.6 Hz, 1H), 6.57 (d, J=8.1, 1H), 4.82 (s, 2H), 4.21 (s, 2H), 3.72 (s, 3H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. dry with materialCombined organics were dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated onto silica gel
  6. custompurified by flash chromatography with ethyl acetate/hexanes as the eluent
  7. additionThe fractions containing the desired product
  8. concentrationwere concentrated to dryness
  9. addition10% Palladium on carbon (500 mg) was added
  10. additiontreated with 50 psi of H2 gas overnight

Sources & evidence

ORD record
ord-d861e61e119e421da429d29f62f6c54f
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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