tert-Butyl acrylate → (E)-3-(6-Amino-5-piperidin-1-ylmethyl-pyridin-3-yl)acrylic acid tert-butyl ester

HRID 1362098

Reaction equation

HRID 1362098 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[C:5]([NH2:8])=[N:6][CH:7]=1.[C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])(=[O:19])[CH:17]=[CH2:18].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(C#N)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:21]([O:20][C:16](=[O:19])/[CH:17]=[CH:18]/[C:2]1[CH:7]=[N:6][C:5]([NH2:8])=[C:4]([CH2:9][N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:3]=1)([CH3:24])([CH3:23])[CH3:22]

Participants

7

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 594569835-Bromo-3-piperidin-1-ylmethyl-pyridin-2-ylamine

Product 1

HCID 59456931(E)-3-(6-Amino-5-piperidin-1-ylmethyl-pyridin-3-yl)acrylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

A solution of 5-bromo-3-piperidin-1-ylmethyl-pyridin-2-ylamine (500 mg, 1.85 mmol), tert-butyl acrylate (0.3 mL, 2.0 mmol), (i-Pr)2EtN (0.5 mL, 2.8 mmol) and P(o-tol)3 (114 mg, 0.37 mmol) in EtCN (10 mL) was de-oxygenated with argon for 30 min. Pd(OAc)2 (43 mg, 0.19 mmol) was added, and the mixture was de-oxygenated for 15 min. The mixture was heated to reflux for 18 h and then allowed to cool. The solvent was removed in vacuo. The residue was partitioned between EtOAc and H2O. The organic layer was washed with H2O and satd NaCl, dried over Na2SO4 and concentrated. Purification by column chromatography (silica gel, CH2Cl2 to 96:4 CH2Cl2/CH3OH) gave the title compound (350 mg, 60%) as a yellow solid: MS (ESI) m/e 318 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 h
  3. temperatureto cool
  4. customThe solvent was removed in vacuo
  5. customThe residue was partitioned between EtOAc and H2O
  6. washThe organic layer was washed with H2O and satd NaCl
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customPurification by column chromatography (silica gel, CH2Cl2 to 96:4 CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-5ba8fdefc565475a8d58ef676427d959
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Linked notes

Loading…