Reaktion #479651

Reaktionsgleichung

triphenylphosphine

Di-tert-butyl azodicarboxylate

(2-fluoropyridin-3-yl)methanol

N-(4-(2,4-difluorophenoxy)phenyl)-N-ethylsulfonylamine

di-tert-butyl azodicarboxylate

→

title compound

Ausbeute 53.0%

N-(4-(2,4-Difluorophenoxy)phenyl)-N-(ethanesulfonyl)-2-fluoropyrid-3-ylmethylamine

Ausbeute 53.0%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added
2. 2
   workup.STIRRINGThis solution was stirred for 24 h after which the suspension
3. 3
   Sonstigethe solids were removed by vacuum filtration
4. 4
   SonstigeThe filtrate solvent was removed under reduced pressure
5. 5
   Sonstigeto provide the crude product as a yellow oil
6. 6
   SonstigeThis oil was purified by medium pressure liquid chromatography on silica gel
7. 7
   Wascheneluting with hexanes/ethyl acetate (7:3)
8. 8
   Sonstigeto provide a colorless oil
9. 9
   SonstigeThis oil was triturated with hexanes/ethyl acetate (4-5 mL)

Vorschrift

Di-tert-butyl azodicarboxylate (0.36 g, 1.57 mmol) was added to a suspension of (2-fluoropyridin-3-yl)methanol (10, 0.20 g, 1.57 mmol), N-(4-(2,4-difluorophenoxy)phenyl)-N-ethylsulfonylamine (0.49 g, 1.56 mmol) and polystyrene resin-bound triphenylphosphine (0.52 g, 1.57 mmol, ˜3 mmol/g) in anhydrous tetrahydrofuran (5 mL) at 0° C. under nitrogen. The resulting yellow suspension was warmed to room temperature and stirred for 19 h, after which additional polystyrene resin bound triphenylphosphine (0.52 g, 1.57 mmol, ˜3 mmol/g) and di-tert-butyl azodicarboxylate (0.36 g, 1.57 mmol) were added. This solution was stirred for 24 h after which the suspension was diluted with anhydrous tetrahydrofuran (100 mL) and the solids were removed by vacuum filtration. The filtrate solvent was removed under reduced pressure to provide the crude product as a yellow oil. This oil was purified by medium pressure liquid chromatography on silica gel, eluting with hexanes/ethyl acetate (7:3), to provide a colorless oil. This oil was triturated with hexanes/ethyl acetate (4-5 mL) to give the title compound as a white powder (0.28 g, 53%): mp 110-112° C.; TLC Rf (3:2 hexanes/ethyl acetate)=0.44; 1H NMR (300 MHz) 8.11 (m, 1H), 7.90 (m, 1H), 7.24-7.15 (m, 3H), 7.11-7.03 (m, 1H), 6.98-6.86 (m, 2H), 6.84 (d, J=6.8 Hz, 2H), 4.91 (s, 2H), 3.15-3.07 (q, J=7.4 Hz, 2H), 1.43 (t, J=7.4 Hz, 1H) ppm; 13C NMR (75 MHz) 163.3, 161.3, 160.1, 157.8, 156.5, 153.1, 147.5 (d, J=14.9 Hz), 141.7, 139.1, 133.6, 130.5, 123.8 (d, J=9.7 Hz), 122.1, 119.1 (d, J=29.2 Hz), 117.5, 112.0 (d, J=22.9 Hz), 106.0 (t, J=24.3 Hz), 49.1, 46.0, 8.44 ppm; APCI MS m/z 423 [C20H17F3N2O3S+H]+. Anal. Calcd. for C20H17F3N2O3S: C, 56.87; H, 4.06; N, 6.63. Found: C, 56.90; H, 4.10; N, 6.45.

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