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

HRID 2355061
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2355061
[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
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344Dichloromethane
Lösungsmittel

Versuchsvorschrift

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+).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-434134c487e2443dbe9838d8dcafa38b
Quelldatensatz
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07754745B2

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