Triethylamine → 2-{3-[2-(Trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carbonitrile

HRID 2355061Notes

Reaction equation

HRID 2355061 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]2[S:12][C:13]([C:16]([NH2:18])=O)=[CH:14][N:15]=2)[CH2:7]1.C(N(CC)CC)C.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O>C(Cl)Cl>[F:23][C:2]([F:1])([F:24])[C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]2[S:12][C:13]([C:16]#[N:18])=[CH:14][N:15]=2)[CH2:7]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 576528252-{3-[2-(Trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxamide

Product 1

HCID 684535482-{3-[2-(Trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-{3-[2-(trifluoromethyl)phenoxy]pyrrolidin-1-yl}-1,3-thiazole-5-carboxamide (670 mg, 1.9 mmol) and triethylamine (0.92 mL, 6.6 mmol) in CH2Cl2 (25 mL) was cooled with an ice-acetone bath. Triflic anhydride (412 μL, 2.4 mmol) was added dropwise over 10 min. The mixture was stirred for 5 min and then the cooling bath was removed. After further stirring at rt 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. Combi-Flash chromatography (40 g, 40-80% EtOAc in hexanes in 20 min, 35 mL/min, 18 mL/fraction) gave a gum that was triturated with hexanes-Et2O (1:1) to give the title compound as a white powder. 1H NMR (400 MHz, acetone-d6): δ 7.88 (s, 1 H), 7.67 (m, 2 H), 7.41 (d, 1 H), 7.18 (t, 1 H), 5.53 (s, 1 H), 3.99 (m, 1 H), 3.85-3.67 (m, 3 H), 2.63-2.45 (m, 2 H). MS (+ESI) m/z 340 (MH+).

Workup

  1. temperaturewas cooled with an ice-acetone bath
  2. customthe cooling bath was removed
  3. stirringAfter further stirring at rt 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. customCombi-Flash chromatography (40 g, 40-80% EtOAc in hexanes in 20 min, 35 mL/min, 18 mL/fraction) gave a gum that
  10. customwas triturated with hexanes-Et2O (1:1)

Sources & evidence

ORD record
ord-434134c487e2443dbe9838d8dcafa38b
Source dataset
uspto-grants-2010_07
Patent number
US07754745B2

Reaction notes

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