Triethylamine → methyl 3-(N-ethyl-N-methylsulfamoylamino)-2,6-difluorobenzoate

HRID 2196739Notes

Reaction equation

HRID 2196739 reaction equation
C(N([CH2:6][CH3:7])CC)C.[NH2:8][C:9]1[C:10]([F:20])=[C:11]([C:16]([F:19])=[CH:17][CH:18]=1)[C:12]([O:14][CH3:15])=[O:13].[S:21](Cl)(Cl)(=[O:23])=[O:22].[CH3:26][NH:27]CC>C(Cl)Cl>[CH2:6]([N:8]([C:9]1[C:10]([F:20])=[C:11]([C:16]([F:19])=[CH:17][CH:18]=1)[C:12]([O:14][CH3:15])=[O:13])[S:21](=[O:23])(=[O:22])[NH:27][CH3:26])[CH3:7]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12219N-MethylethylamineHCID 24648Sulfuryl chlorideHCID 45480188Methyl 3-amino-2,6-difluorobenzoate

Product 1

HCID 67052525methyl 3-(N-ethyl-N-methylsulfamoylamino)-2,6-difluorobenzoateYield 49.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of triethylamine (0.260 mL, 1.85 mmol) and methyl 3-amino-2,6-difluorobenzoate (0.257 mL, 1.85 mmol) was added dropwise to sulfuryl dichloride (0.156 mL, 1.85 mmol) in DCM (3 mL) at −78° C. After 2 hours, N-methylethanamine (0.304 mL, 3.70 mmol) was added, and the reaction mixture was allowed to warm to room temperature overnight. The solvent was concentrated under reduced pressure, and the residue was taken up in NaOH (2 mL, 1M) and washed with EtOAc. The aqueous pH was lowered to below 3 and extracted with EtOAc (3×5 mL). The combined organic layers were dried over sodium sulfate, decanted and concentrated under reduced pressure. The residue was purified via silica gel chromatography eluting with 7:3 hexane-EtOAc to afford impure methyl 3-(N-ethyl-N-methylsulfamoylamino)-2,6-difluorobenzoate (0.280 g, 49.0% yield).

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. washwashed with EtOAc
  3. extractionextracted with EtOAc (3×5 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified via silica gel chromatography
  8. washeluting with 7:3 hexane-EtOAc

Sources & evidence

ORD record
ord-76973eb691b2446eb5595b674accc98b
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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