Reaktion #88956

Reaktionsgleichung

2,2,2-trichloroethylchloroformate

Intermediate 74f

3-tert-Butyl-1′-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-3′-triisopropylsilanyloxymethyl-1′H-[1,4′]bipyrazolyl-5-ylamine

NaOH

2,2,2-trichloroethylchloroformate

2,2,2-trichloroethylchloroformate

→

title compound

Ausbeute 80.0%

{3-tert-Butyl-1′-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-3′-triisopropylsilanyloxymethyl-1′H-[1,4′]bipyrazolyl-5-yl}-carbamic acid 2,2,2-trichloro-ethyl ester

Ausbeute 80.0%

Lösungsmittel

EtOAc

EtOAc

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred over the weekend
2. 2
   workup.STIRRINGstirred for 1 h
3. 3
   Sonstigethe layers were separated
4. 4
   ExtraktionThe aqueous layer was then extracted with EtOAc (2×)
5. 5
   WaschenThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution, and brine
6. 6
   Trocknendried (Na2SO4)
7. 7
   Filtrationfiltered
8. 8
   Sonstigeevaporated in vacuo
9. 9
   SonstigeThe residue was purified by FCC

Vorschrift

To a solution of Intermediate 74f (0.44 g, 0.85 mmol) in EtOAc (5 mL) was added 1N aqueous NaOH solution (1.7 mL, 1.7 mmol) followed by 2,2,2-trichloroethylchloroformate (0.13 mL, 0.93 mmol). The reaction was stirred at RT for 4 h then treated with another portion of 2,2,2-trichloroethylchloroformate (35 μL, 0.25 mmol) and stirred over the weekend. The reaction was treated with another portion of 2,2,2-trichloroethylchloroformate (35 μL, 0.25 mmol) and stirred for 1 h then diluted with EtOAc and water and the layers were separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-4% MeOH in DCM, to give the title compound (0.47 g, 80%). 1H NMR (300 MHz, CDCl3): 0.96 (18H, d, J=6.8 Hz), 1.01-1.17 (3H, m), 1.25 (9H, s), 1.38-1.51 (4H, m), 1.54-1.75 (2H, m), 3.36-3.45 (1H, m), 3.58-3.68 (1H, m), 3.68-3.77 (1H, m), 3.97-4.07 (1H, m), 4.24 (2H, t, J=4.7 Hz), 4.51 (1H, t, J=3.2 Hz), 4.59 (2H, s), 4.69-4.73 (2H, m), 6.26 (1H, s), 7.63 (1H, s), 7.74 (1H, s).

Quelle