Triphenylphosphine → 1-Benzyl 4-tert-butyl 2-(2-(pyridin-3-yl)ethyl)piperazine-1,4-dicarboxylate

HRID 1487708Notes

Reaction equation

HRID 1487708 reaction equation
C12BC(CCC1)CCC2.[CH:10]([CH:12]1[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15][CH2:14][N:13]1[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[CH2:11].Br[C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:38]1[CH:39]=[CH:40][CH:41]=[C:36]([CH2:11][CH2:10][CH:12]2[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])[CH2:15][CH2:14][N:13]2[C:25]([O:27][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[O:26])[CH:37]=1

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 122863-BromopyridineHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 596714681-Benzyl 4-tert-butyl 2-vinylpiperazine-1,4-dicarboxylate

Product 1

HCID 596715351-Benzyl 4-tert-butyl 2-(2-(pyridin-3-yl)ethyl)piperazine-1,4-dicarboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

9-Borabicyclo[3.3.1]nonane (0.5M solution in THF, 54 mL, 27 mmol) was added to 1-benzyl 4-tert-butyl 2-vinylpiperazine-1,4-dicarboxylate (2.33 g, 6.73 mmol). After 3 h, 3-bromopyridine (0.99 mL, 10.1 mmol), triphenylphosphine (0.53 g, 2.0 mmol), and tetrakis(triphenylphosphine) palladium(0) (0.311 g, 0.27 mmol) were added. Sodium hydroxide (1N aqueous solution, 16.8 mL, 16.8 mmol) was added slowly. Once bubbling ceased, the reaction mixture was heated to reflux overnight. Upon cooling to rt, the reaction mixture was diluted with water (200 mL) and extracted with EtOAc (3×200 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (10 to 40% EtOAc in Hexane gradient) gave 1.79 g (63%) of the desired product as a thick oil. Rf=0.57 in 80% EtOAc/Hexane. LC-MS: RT=7.69 min., [M+H]+=426.2. The material was contaminated with ˜15% triphenylphosphine, and was used without further purification.

Workup

  1. customOnce bubbling
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux overnight
  4. additionthe reaction mixture was diluted with water (200 mL)
  5. extractionextracted with EtOAc (3×200 mL)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by column chromatography (10 to 40% EtOAc in Hexane gradient)

Sources & evidence

ORD record
ord-5bf08afcd1e745e18c13f92aa0e7f6f5
Source dataset
uspto-grants-2016_08
Patent number
US09428522B2

Reaction notes

Loading…