Acetic Anhydride → HCID 59731922, compound

HRID 132297Notes

Reaction equation

HRID 132297 reaction equation
[NH2:1][C:2]1[C:3]([CH3:11])=[C:4]([CH2:9][OH:10])[CH:5]=[CH:6][C:7]=1[CH3:8].[C:12](=[O:15])([O-])O.[Na+].ICl.[I-:19].[C:20](OC(=O)C)(=[O:22])[CH3:21].[CH3:27]N(C1C=CC=CN=1)C>CO.ClCCl>[C:20]([NH:1][C:2]1[C:3]([CH3:11])=[C:4]([C:5]([I:19])=[CH:6][C:7]=1[CH3:8])[CH2:9][O:10][C:12](=[O:15])[CH3:27])(=[O:22])[CH3:21]

Participants

9

Reactant 6

HCID 7918Acetic AnhydrideHCID 218852-DimethylaminopyridineHCID 24640Iodine chlorideHCID 30165Iodide IonHCID 516892Sodium BicarbonateHCID 45116648(3-Amino-2,4-dimethylphenyl)methanol

Product 1

HCID 59731922HCID 59731922, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a well stirred solution of (3-amino-2,4-dimethyl-phenyl)-methanol (1.5 g) in methanol (70 mL) and solid sodium hydrogen carbonate (4.0 eq) was added a 1.0 M solution of iodine monochloride dropwise over a period of 5 min at 0° C. The cooling bath was removed after the addition of iodine monochloride. The reaction mixture was brought to room temperature and stirring continued for another 1 h. The reaction mixture was concentrated to remove most of methanol, diluted with dichloromethane (50 mL) and washed with 10% solution of sodium thiosulfate and dried (Na2SO4). The desired compound was purified by trituration with dichloromethane and hexane to give in 1.9 g of iodide. The iodide was then treated with dichloromethane (100 mL) followed by acetic anhydride (4 eq) and catalytic amount of dimethylaminopyridine and stirred for a period of 12 h at room temperature. The reaction mixture was then washed with aqueous sodium hydrogen carbonate, 1.0 M hydrochloric acid and dried (Na2SO4). The desired compound was triturated with dichloromethane and hexane to give acetic acid 3-acetylamino-6-iodo-2,4-dimethyl-benzyl ester in 95% yield. 1H NMR (300 MHz, CDCl3): in δ 7.68 (s, 1 H), 6.68 (s, 1 H), 2.28 (s, 3 H), 2.25 (s, 3 H), 2.18 (s, 3 H), 2.07(s, 3 H); MS (ESI) 384 (M+Na); Rf=1.12.

Workup

  1. customThe cooling bath was removed
  2. additionafter the addition of iodine monochloride
  3. customwas brought to room temperature
  4. concentrationThe reaction mixture was concentrated
  5. customto remove most of methanol
  6. additiondiluted with dichloromethane (50 mL)
  7. washwashed with 10% solution of sodium thiosulfate
  8. dry with materialdried (Na2SO4)
  9. customThe desired compound was purified by trituration with dichloromethane and hexane
  10. customto give in 1.9 g of iodide
  11. stirringstirred for a period of 12 h at room temperature
  12. washThe reaction mixture was then washed with aqueous sodium hydrogen carbonate, 1.0 M hydrochloric acid
  13. dry with materialdried (Na2SO4)
  14. customThe desired compound was triturated with dichloromethane and hexane

Sources & evidence

ORD record
ord-613810cc4fde41d2a93a44e031ca6e15
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

Loading…