Methyl iodide → 2-Chloro-6-methoxymethylaniline

HRID 619964Notes

Reaction equation

HRID 619964 reaction equation
[NH2:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].[CH2:11]([Li])CCC.CI>C1COCC1.CCCCCC>[Cl:10][C:9]1[CH:8]=[CH:7][CH:6]=[C:3]([CH2:4][O:5][CH3:11])[C:2]=1[NH2:1]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 14155407(2-Amino-3-chlorophenyl)methanolHCID 178418339Butyllithium

Product 1

HCID 141554082-Chloro-6-methoxymethylanilineYield 25.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A solution of 4.00 g (25.4 mmol) of 2-amino-3-chlorobenzyl alcohol in 30 ml of dry THF was cooled to -78° C., treated with 16.7 ml (26.7 mmol) of 1.60M n-butyllithium in hexane, warmed to 0°-5° C., treated with 3.61 g (25.4 mmol) of methyl iodide and heated at reflux for 5.5 hours. The solvent was removed by evaporation at reduced pressure. The residue was partitioned between 175 ml of ether and water, and the organic phase was separated and dried (MgSO4). The solvent was removed by evaporation at reduced pressure, and the residue was purified by HPLC eluting with EtOAc and hexane (5:95, v/v) to afford 1.1 g of the desired product as a pale brown oil. IR and 1H NMR spectra were in agreement with the assigned structure.

Workup

  1. temperaturewarmed to 0°-5° C.
  2. temperatureheated
  3. temperatureat reflux for 5.5 hours
  4. customThe solvent was removed by evaporation at reduced pressure
  5. customThe residue was partitioned between 175 ml of ether and water
  6. customthe organic phase was separated
  7. dry with materialdried (MgSO4)
  8. customThe solvent was removed by evaporation at reduced pressure
  9. customthe residue was purified by HPLC
  10. washeluting with EtOAc and hexane (5:95

Sources & evidence

ORD record
ord-61e2cf7cc44043bcbde264a0bc570717
Source dataset
uspto-grants-1989_04
Patent number
US04818273

Reaction notes

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