Dichloromethane → Phenylmethyl 3-[bis(propylsulfonyl)amino]-6-chloro-2-fluorobenzoate

HRID 1943848Notes

Reaction equation

HRID 1943848 reaction equation
[NH2:1][C:2]1[C:3]([F:19])=[C:4]([C:15]([Cl:18])=[CH:16][CH:17]=1)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].ClCCl.[CH2:23]([S:26](Cl)(=[O:28])=[O:27])[CH2:24][CH3:25]>>[Cl:18][C:15]1[C:4]([C:5]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6])=[C:3]([F:19])[C:2]([N:1]([S:26]([CH2:23][CH2:24][CH3:25])(=[O:28])=[O:27])[S:26]([CH2:23][CH2:24][CH3:25])(=[O:28])=[O:27])=[CH:17][CH:16]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 662791-Propanesulfonyl chlorideHCID 58087305Benzyl 3-amino-6-chloro-2-fluorobenzoate

Product 1

HCID 58095375Phenylmethyl 3-[bis(propylsulfonyl)amino]-6-chloro-2-fluorobenzoateYield 72.7%

Conditions

Temperature
0 °C

Procedure

Benzyl 3-amino-6-chloro-2-fluorobenzoate (4.3 g, 15.37 mmol) was dissolved in dry dichloromethane (270 mL) Triethylamine (5.36 mL, 2.5 eq.) was added, and the mixture was chilled to 0° C. Propane-1-sulfonyl chloride (3.63 mL, 32.3 mmol, 2.1 eq.) was then added via syringe, and a precipitate resulted. Once the addition was complete, the mixture was allowed to warm to room temperature, and the starting material was consumed as determined by TLC (3:1 hexane:ethyl acetate). The mixture was then diluted with dichloromethane (200 mL), washed with 2M aqueous HCl (2×100 mL), saturated Na2HCO3 solution, dried over sodium sulfate and concentrated. The resulting residue was purified on a 65 Biotage chromatography system (40% ethyl acetate/hexane) to produce benzyl 6-chloro-2-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate (5.5 g, 72%) as an oil that slowly solidified upon standing. NMR (CDCl3, 400 MHz) δ 7.28-7.45 (m, 7H), 5.42 (s, 2H), 3.58-3.66 (m, 2H), 3.43-3.52 (m, 2H), 1.08 (t, 6H, J=8).

Workup

  1. additionwas added
  2. customa precipitate resulted
  3. additionOnce the addition
  4. temperatureto warm to room temperature
  5. customthe starting material was consumed
  6. additionThe mixture was then diluted with dichloromethane (200 mL)
  7. washwashed with 2M aqueous HCl (2×100 mL), saturated Na2HCO3 solution
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe resulting residue was purified on a 65 Biotage chromatography system (40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4087496d66e54ad1aea11001482ebfa3
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

Loading…