Trifluoromethanesulfonic anhydride → 2-{4-[2-(Trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carbonitrile

HRID 561201Notes

Reaction equation

HRID 561201 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:13][C:14]([C:17]([NH2:19])=O)=[CH:15][N:16]=2)[CH2:8][CH2:7]1.O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O>C(Cl)Cl>[F:24][C:2]([F:1])([F:25])[C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:13][C:14]([C:17]#[N:19])=[CH:15][N:16]=2)[CH2:8][CH2:7]1

Participants

4

Reactant 2

HCID 67749Trifluoromethanesulfonic anhydrideHCID 468806672-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)thiazole-5-carboxamide

Product 1

HCID 666968312-{4-[2-(Trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3-thiazole-5-carboxamide (4 g, 10.8 mmol) in CH2Cl2 (100 mL) was cooled with an ice-acetone bath. Tf2O (2.0 mL, 11.9 mmol) was then added dropwise over about 10 min. The mixture was stirred for 5 min and then the cooling bath was removed. After further stirring at room temperature for 15 min, the mixture was quenched with water and extracted twice with CH2Cl2. The combined CH2Cl2 extracts were washed twice with diluted brine, dried (Na2SO4) and concentrated. The crude material was purified by column chromatography on silica gel (eluting with 40% EtOAc/hexanes) to give the title compound as a pale yellow solid.

Workup

  1. temperaturewas cooled with an ice-acetone bath
  2. customthe cooling bath was removed
  3. stirringAfter further stirring at room temperature for 15 min
  4. customthe mixture was quenched with water
  5. extractionextracted twice with CH2Cl2
  6. washThe combined CH2Cl2 extracts were washed twice with diluted brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography on silica gel (eluting with 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c67423d2b129458e80044b0ad1c8b353
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

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