Hydrochloric Acid → Cyclopropanesulfonic acid 3-(2',4',5'-trifluoro-biphenyl-4-yloxymethyl)-benzoylamide

HRID 1665259Notes

Reaction equation

HRID 1665259 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=2)[C:21]([OH:23])=O)=[CH:12][CH:11]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:39]1([S:42]([NH2:45])(=[O:44])=[O:43])[CH2:41][CH2:40]1.C1CCN2C(=NCCC2)CC1.Cl>C1COCC1.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C:10]1[CH:11]=[CH:12][C:13]([O:16][CH2:17][C:18]2[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=2)[C:21]([NH:45][S:42]([CH:39]2[CH2:41][CH2:40]2)(=[O:44])=[O:43])=[O:23])=[CH:14][CH:15]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 582711903-(2',4',5'-Trifluoro-biphenyl-4-yloxymethyl)-benzoic acid

Product 1

HCID 52933064Cyclopropanesulfonic acid 3-(2',4',5'-trifluoro-biphenyl-4-yloxymethyl)-benzoylamideYield 40.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-(2′,4′,5′-trifluoro-biphenyl-4-yloxymethyl)-benzoic acid (5.0 g, 13.96 mmol) in THF (100 mL) was treated with CDI (3.37 g, 20.78 mmol), heated at 50° C. for 30 min, cooled to room temperature, added cyclopropanesulfonamide (1.86 g, 15.35 mmol) and DBU (4.2 mL, 28.08 mmol) and heated at 60° C. for 17 h. The reaction mixture was cooled to room temperature, treated with aqueous 2N HCl (50 mL), stirred for 10 min, added water (50 mL) and extracted with ethyl acetate (3×100 mL). The organic layers were combined, washed with conc. HCl (20 mL), water (50 mL), 1/1 water/brine (50 mL), brine (50 mL), dried (MgSO4), filtered, concentrated and recrystallized from methanol to give cyclopropanesulfonic acid 3-(2′,4′,5′-trifluoro-biphenyl-4-yloxymethyl)-benzoylamide (2.58 g, 40.1%) as a white solid. LC-MS (ES) calculated for C23F18F3NO4S, 461.46; found m/z 460 [M−H]−.

Workup

  1. temperaturecooled to room temperature
  2. temperatureheated at 60° C. for 17 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. washwashed with conc. HCl (20 mL), water (50 mL), 1/1 water/brine (50 mL), brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customrecrystallized from methanol

Sources & evidence

ORD record
ord-498be165af8f4da6b08c29df830b086e
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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