반응 #743735

반응 방정식

5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

(S)-3-amino-Boc-piperidine

BINAP

sodium tert-butoxide

→

title compound

수율 81.0%

(3S)-tert-Butyl 3-(1-(Tetrahydro-2H-pyran-2-yl)-1H-indazol-5-ylamino)piperidine-1-carboxylate

수율 81.0%

반응 조건

후처리

1. 1
   workup.ADDITIONThe flask containing the solids
2. 2
   기타was then evacuated
3. 3
   workup.ADDITIONback-filled with nitrogen three times
4. 4
   기타to degas
5. 5
   workup.ADDITIONPyridine (200 mL) was then added
6. 6
   기타the flask was again purged three times with vacuum and nitrogen
7. 7
   온도In the morning, the reaction was cooled to room temperature
8. 8
   workup.ADDITIONdiluted with 250 mL EtOAc
9. 9
   세척washed three times with 250 mL portions of 10% NaHSO4
10. 10
    기타the organic phase was evaporated
11. 11
    workup.DISSOLUTIONThe residue was dissolved in toluene
12. 12
    세척The column was washed with 5 column volumes of heptane
13. 13
    세척after which the desired product was eluted with EtOAc/heptane

실험 절차

A 500 mL round bottom flask with a stirbar was charged with 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (28.0 g, 0.0996 mol, 1.00 eq), (S)-3-amino-Boc-piperidine (21.75 g, 0.109 mol, 1.09 eq), tris(dibenzylideneacetone)dipalladium (4.75 g, 5.18 mmol, 0.052 eq), racemic BINAP (7.44 g, 12.0 mmol, 0.12 eq), and sodium tert-butoxide (28.7 g, 0.299 mol, 3.00 eq). The flask containing the solids was then evacuated and back-filled with nitrogen three times to degas. Pyridine (200 mL) was then added, and the flask was again purged three times with vacuum and nitrogen. The dark greenish mixture was then stirred at 55° C. overnight under a nitrogen atmosphere. In the morning, the reaction was cooled to room temperature, diluted with 250 mL EtOAc, washed three times with 250 mL portions of 10% NaHSO4, and the organic phase was evaporated. The residue was dissolved in toluene and loaded onto a silica column that had been packed with heptane. The column was washed with 5 column volumes of heptane, after which the desired product was eluted with EtOAc/heptane, to provide the title compound as a pale yellow foam (2.4 g, 81%).

출처