2,6-Lutidine → 3-Amino-5-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-4-chlorobenzonitrile

HRID 1430799Notes

Reaction equation

HRID 1430799 reaction equation
[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]2[C:16]([Cl:31])=[C:17]([NH:23]C(=O)OC(C)(C)C)[CH:18]=[C:19]([C:21]#[N:22])[CH:20]=2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>ClCCl>[NH2:23][C:17]1[CH:18]=[C:19]([CH:20]=[C:15]([N:12]2[CH2:11][CH2:10][CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3])[CH2:14][CH2:13]2)[C:16]=1[Cl:31])[C:21]#[N:22]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 86708480Tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate

Product 1

HCID 867084823-Amino-5-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-4-chlorobenzonitrileYield 73.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(I13B): To a round bottom flask charged with tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (I13A) (3.27 g, 7.02 mmol) in dichloromethane (35.1 ml) and cooled to 0° C. was added 2,6-lutidine (2.451 ml, 21.05 mmol). Trimethylsilyl trifluoromethanesulfonate (3.80 ml, 21.05 mmol) was added dropwise over 5 min. After 1 h, the reaction mixture was quenched by the addition of saturated aqueous sodium bicarbonate and dichloromethane. The mixture was transferred to a separatory funnel and the aqueous layer was extracted with dichloromethane (3×). The combined organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by column chromatography on the Isco system (120 g, 0-50% EtOAc/CH2Cl2). 3-amino-5-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-4-chlorobenzonitrile (I13B) (1.892 g) was isolated as a sticky yellow oil.

Workup

  1. customthe reaction mixture was quenched by the addition of saturated aqueous sodium bicarbonate and dichloromethane
  2. customThe mixture was transferred to a separatory funnel
  3. extractionthe aqueous layer was extracted with dichloromethane (3×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by column chromatography on the Isco system (120 g, 0-50% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-d7ea757e20ab44da92a2f9b3fb3b7c0c
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

Loading…