Cesium carbonate → 1,1-Dimethylethyl 4-[(3-cyanophenyl)amino]-1-piperidinecarboxylate

HRID 43344

Reaction equation

HRID 43344 reaction equation
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:53][CH:54]1[CH2:59][CH2:58][N:57]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:56][CH2:55]1.Br[C:68]1[CH:69]=[C:70]([CH:73]=[CH:74][CH:75]=1)[C:71]#[N:72]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:71]([C:70]1[CH:69]=[C:68]([NH:53][CH:54]2[CH2:55][CH2:56][N:57]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:58][CH2:59]2)[CH:75]=[CH:74][CH:73]=1)#[N:72]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 233813-BromobenzonitrileHCID 634876Binap, (A+-)-HCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 252237961,1-Dimethylethyl 4-[(3-cyanophenyl)amino]-1-piperidinecarboxylateYield 82.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of BINAP (560 mg, 0.9 mmol), palladium acetate (135 mg, 0.6 mmol) and cesium carbonate (2.932 g, 9 mmol) in 1,4-dioxane (10 ml) was sonicated for 50 minutes. 1,1-Dimethylethyl 4-amino-1-piperidinecarboxylate (1.2 g, 6 mmol) and 3-bromobenzonitrile (1.638 g, 9 mmol) were added and the mixture heated to 105° C. overnight under an argon atmosphere. On cooling, the solvent was removed in vacuo and the residue partitioned between water (100 ml) and EtOAc (100 ml). The organic layer was separated, dried and concentrated and the crude product purified by chromatography. Elution with a 0-50% Et2O/petroleum ether gradient gave the title compound as a white solid (1.49 g). δH (CDCl3, 250 MHz) 7.22 (2H, t), 6.95 (1H, dd), 6.77 (2H, m), 4.07 (2H, m), 3.77 (1H, m), 3.41 (1H, m), 3.20 (1H, m), 2.93 (2H, m), 2.03 (2H, m), 1.47 (9H, s), 1.34 (2H, m). MS (ES): MH+ 302.

Workup

  1. customwas sonicated for 50 minutes
  2. temperatureOn cooling
  3. customthe solvent was removed in vacuo
  4. customthe residue partitioned between water (100 ml) and EtOAc (100 ml)
  5. customThe organic layer was separated
  6. customdried
  7. concentrationconcentrated
  8. customthe crude product purified by chromatography
  9. washElution with a 0-50% Et2O/petroleum ether gradient

Sources & evidence

ORD record
ord-9a54a3b366f844a18f94b9db04f87ad0
Source dataset
uspto-grants-2013_09
Patent number
US08536182B2

Linked notes

Loading…