2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 178527323, compound

HRID 853123Notes

Reaction equation

HRID 853123 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]([C@H:16]1[CH2:21][CH2:20][C@H:19]([NH:22][S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH2:18][CH2:17]1)([O:8][Si](CC)(CC)CC)[C:4]([F:7])([F:6])[F:5].[Li]CCCC.[F:39][C:40]([F:51])([F:50])[CH2:41]OS(C(F)(F)F)(=O)=O>C1COCC1.CCCCCC>[F:39][C:40]([F:51])([F:50])[CH2:41][N:22]([C@H:19]1[CH2:18][CH2:17][C@H:16]([C:3]([OH:8])([C:2]([F:1])([F:33])[F:32])[C:4]([F:7])([F:5])[F:6])[CH2:21][CH2:20]1)[S:23]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)(=[O:24])=[O:25]

Participants

6

Reactant 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 178418339ButyllithiumHCID 178477576HCID 178477576, compound

Product 1

HCID 178527323HCID 178527323, compoundYield 40.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-40 °C

Procedure

A solution of 0.45 g (0.87 mmol) of trans N-[4-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-cyclohexyl]-benzenesulfonamide in 5 mL of dry THF was cooled to −78° C. and treated dropwise with 0.7 mL (1.13 mmol) of a 1.6M solution of nBuLi in hexane. The solution was warmed to −40° C., treated with 1.0 g (4.33 mmol) of trifluoro-methanesulfonic acid 2,2,2-trifluoro-ethyl ester and then allowed to reach RT. The mixture was stirred for 30 min at RT and then refluxed for 2 hrs. The solvent was evaporated, the residue redissolved in 2 mL of THF and treated with an excess of TBAF. Distribution between a saturated aqueous solution of NH4Cl and Et2O, drying of the combined organic phases and chromatography on silica gel with heptane/EtOAc 2:1 gave 0.17 g (40%) of trans N-(2,2,2-trifluoro-ethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-cyclohexyl]-benzenesulfonamide as a light yellow oil, MS: 486 (M−H)−.

Workup

  1. customto reach RT
  2. temperaturerefluxed for 2 hrs
  3. customThe solvent was evaporated
  4. dissolutionthe residue redissolved in 2 mL of THF
  5. additiontreated with an excess of TBAF
  6. dry with materialDistribution between a saturated aqueous solution of NH4Cl and Et2O, drying of the combined organic phases and chromatography on silica gel with heptane/EtOAc 2:1

Sources & evidence

ORD record
ord-0d68d684260746cd8be45a6fe74f18c9
Source dataset
uspto-grants-2007_08
Patent number
US07253282B2

Reaction notes

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