Trifluoromethanesulfonic anhydride → HCID 178500919, compound

HRID 2118228Notes

Reaction equation

HRID 2118228 reaction equation
[OH:1][CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.O[C@H:38]1[CH2:43][CH2:42][C@H:41]([N:44]([CH3:58])[S:45]([C:48]2[CH:53]=[CH:52][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:50][CH:49]=2)(=[O:47])=[O:46])[CH2:40][CH2:39]1>C(Cl)Cl.[N+](C)([O-])=O.CCOC(C)=O.OS([O-])(=O)=O.[K+]>[CH3:7][O:6][C:4](=[O:5])[CH2:3][CH2:2][O:1][C@H:38]1[CH2:39][CH2:40][C@H:41]([N:44]([CH3:58])[S:45]([C:48]2[CH:53]=[CH:52][C:51]([C:54]([F:56])([F:55])[F:57])=[CH:50][CH:49]=2)(=[O:47])=[O:46])[CH2:42][CH2:43]1

Participants

9

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 685102,6-Di-tert-butylpyridine2×HCID 80252Propanoic acid, 3-hydroxy-, methyl esterHCID 178484845HCID 178484845, compound

Product 1

HCID 178500919HCID 178500919, compoundYield 95.7%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 6375NitromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516920Potassium bisulfateSolvent

Procedure

To a solution of 0.62 g (5.9 mmol) of methyl beta-hydroxypropionate in 4.5 mL of CH2Cl2 was added 1.4 mL (6.4 mmol, 2.4 eq) of 2,6-di-tert-butylpyridine, followed by 1.03 mL (6.2 mmol, 2.4 eq) of trifluoromethane sulfonic acid anhydride at 0° C. The solution was stirred at that temperature for 2.5 h, was concentrated and the residue was dissolved in 5 mL of nitromethane. To this solution 1 g (2.96 mmol) of trans-N-(4-hydroxy-cyclohexyl)-N-methyl-4-trifluoromethyl-benzenesulfonamide and 1.3 mL (5.9 mmol, 2.0 eq) of 2,6-di-tert-butylpyridine in 10 mL of nitromethane were added. The solution was stirred at 60° C. for 3 h, diluted with EtOAc and 1M KHSO4. The inorganic phase was extracted with EtOAc, the combined organic phases were washed with a saturated aqueous solution of NaHCO3 and brine, were dried over Na2SO4 and evaporated. Column chromatography on silica gel with EtOAc/n-hexane 1:3 gave 1.2 g (95%) of trans-3-{4-[methyl-(4-trifluoromethyl-benzenesulfonyl)-amino]-cyclohexyloxy}-propionic acid methyl ester as light yellow oil, MS: 424 (MH+).

Workup

  1. concentrationwas concentrated
  2. dissolutionthe residue was dissolved in 5 mL of nitromethane
  3. stirringThe solution was stirred at 60° C. for 3 h
  4. extractionThe inorganic phase was extracted with EtOAc
  5. washthe combined organic phases were washed with a saturated aqueous solution of NaHCO3 and brine
  6. dry with materialwere dried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-b7bd2a4e71854ac7aeb7b4a48a2a7fcd
Source dataset
uspto-grants-2008_10
Patent number
US07442791B2

Reaction notes

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