1,1-Dichloroethane → tert-butyl 5-(3-amino-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

HRID 921811Notes

Reaction equation

HRID 921811 reaction equation
C(OC([NH:8][C:9]1[C:10]([Cl:33])=[C:11]([N:17]2[CH2:22][CH2:21][CH:20]3[N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25][CH:19]3[CH2:18]2)[CH:12]=[C:13]([C:15]#[N:16])[CH:14]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.ClC(Cl)C.C(N(CC)CC)C.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>ClCCl>[NH2:8][C:9]1[C:10]([Cl:33])=[C:11]([N:17]2[CH2:22][CH2:21][CH:20]3[N:23]([C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[CH2:24][CH2:25][CH:19]3[CH2:18]2)[CH:12]=[C:13]([C:15]#[N:16])[CH:14]=1

Participants

7

Reactant 5

HCID 63651,1-DichloroethaneHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 89923255tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

Product 1

HCID 89923100tert-butyl 5-(3-amino-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylateYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl 5-(3-((tert-butoxycarbonyl)amino)-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (358 mg, 0.751 mmol) was treated with 25% TFA in dichloroethane (2 ml, 6.49 mmol) at room temperature for 1 h. Solvent was evaporated in vacuo and the residue was diluted with dichloromethane and washed with water and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude intermediate was dissolved in dichloromethane (10 mL). Triethylamine (0.209 ml, 1.501 mmol) and BOC anhydride (0.261 ml, 1.126 mmol) were added subsequently. The reaction mixture was stirred at room temperature for 1 h and the reaction was complete. The reaction mixture was diluted with dichloromethane and washed with saturated sodium bicarbonate. The aqueous layer was extracted with dichloromethane two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 10-30% ethyl acetate/hexanes) to give tert-butyl 5-(3-amino-2-chloro-5-cyanophenyl)octahydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (266 mg) as a colorless oil.

Workup

  1. customSolvent was evaporated in vacuo
  2. additionthe residue was diluted with dichloromethane
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionthe crude intermediate was dissolved in dichloromethane (10 mL)
  8. washwashed with saturated sodium bicarbonate
  9. extractionThe aqueous layer was extracted with dichloromethane two more times
  10. dry with materialThe combined organic layers were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customthe crude product was purified by flash chromatography on silica gel using
  14. washan automated ISCO system (40 g column, eluting with 10-30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-35aa67f3d232469caa05c6e46a09fbdd
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…