Oxalyl chloride → N-(4-Bromo-2-fluoro-benzyl)-2-methoxy-4-methylsulfanyl-benzamide

HRID 457947Notes

Reaction equation

HRID 457947 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]([S:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.Cl.[Br:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[C:33]([F:39])[CH:32]=1>ClCCl.CN(C)C=O>[Br:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH:36][C:5](=[O:7])[C:4]2[CH:8]=[CH:9][C:10]([S:12][CH3:13])=[CH:11][C:3]=2[O:2][CH3:1])=[C:33]([F:39])[CH:32]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 6433294-(Methylthio)-o-anisic acidHCID 184681974-Bromo-2-fluorobenzylamine hydrochloride

Product 1

HCID 18468171N-(4-Bromo-2-fluoro-benzyl)-2-methoxy-4-methylsulfanyl-benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-methoxy-4-(methylthio)benzoic acid (5.0 g, 25.2 mmol) in dichloromethane (50 mL) was cooled to 0° C. and treated with oxalyl chloride (6.6 mL, 75.6 mmol). A drop of N,N-dimethylformamide was added and the reaction was heated to a gentle reflux for 2 h. After cooling to room temperature, the solution was concentrated in vacuo to remove the excess oxalyl chloride, diluted with dichloromethane (53 mL) and cooled to 0° C. The resulting solution was treated with N,N-diisopropylethylamine (11.6 mL, 67 mmol) and 4-bromo-2-fluorobenzylamine hydrochloride (9.7 g, 40.2 mmol). The resulting solution was stirred at room temperature overnight, concentrated in vacuo, diluted with ethyl acetate and successively washed with 2 N HCl and saturated NaCl. The organic layer was dried over MgSO4, filtered and concentrated. Rf 0.43 (40% ethyl acetate in heptane); 1H NMR (DMSO-d6 300 MHz) δ 8.63 (t, J=6 Hz, 1 H), 7.70 (d, J=8.1 Hz, 1 H), 7.50 (dd, J1=9.6 Hz, J2=2.1 Hz, 1 H), 7.38 (dd, J1=8.4 Hz, J2=2.0 Hz, 1 H), 7.28 (t, J=8.4 Hz, 1 H), 6.94 (br s, 1 H), 6.89 (dd, J1=5.7 Hz, J2=1.7 Hz, 1 H), 4.46 (d, J=6 Hz, 2 H), 3.91 (s, 3 H), 2.51 (s, 3 H).

Workup

  1. temperaturethe reaction was heated to
  2. temperaturea gentle reflux for 2 h
  3. concentrationthe solution was concentrated in vacuo
  4. customto remove the excess oxalyl chloride
  5. additiondiluted with dichloromethane (53 mL)
  6. temperaturecooled to 0° C
  7. concentrationconcentrated in vacuo
  8. additiondiluted with ethyl acetate
  9. washsuccessively washed with 2 N HCl and saturated NaCl
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-c826dc64d1174dc4a75910206bfd5d42
Source dataset
uspto-grants-2007_03
Patent number
US07189749B2

Reaction notes

Loading…