Pyridine → 5-Tert-butyldimethylsilyloxy-2-(phthalimido)-n-[1-(4-pyridyl)piperidin-4-ylcarbonyl]aniline

HRID 427696Notes

Reaction equation

HRID 427696 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[Si:20]([O:27][C:28]1[CH:29]=[CH:30][C:31]([N:35]2[C:39](=[O:40])[C:38]3=[CH:41][CH:42]=[CH:43][CH:44]=[C:37]3[C:36]2=[O:45])=[C:32]([CH:34]=1)[NH2:33])([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21].N1C=CC=CC=1>C(Cl)Cl.C(Cl)Cl.CO>[Si:20]([O:27][C:28]1[CH:29]=[CH:30][C:31]([N:35]2[C:36](=[O:45])[C:37]3=[CH:44][CH:43]=[CH:42][CH:41]=[C:38]3[C:39]2=[O:40])=[C:32]([CH:34]=1)[NH:33][C:13]([CH:10]1[CH2:9][CH2:8][N:7]([C:4]2[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=2)[CH2:12][CH2:11]1)=[O:15])([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 12682891-(Pyridin-4-yl)piperidine-4-carboxylic acidHCID 181744945-(Tert-butyldimethylsilyloxy)-2-phthalimidoaniline

Product 1

HCID 181745985-Tert-butyldimethylsilyloxy-2-(phthalimido)-n-[1-(4-pyridyl)piperidin-4-ylcarbonyl]anilineYield 76.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 21226129Dichloromethane methanolSolvent

Procedure

1-(4-Pyridyl)piperidine-4-carboxylic acid (176 mg, 0.85 mmol) and thionyl chloride (93 mL, 1.28 mmol) in 5 mL methylene chloride were heated under reflux for 2 h. The mixture was allowed to cool, concentrated in vacuo to a white foam and dried under vacuum. The foam was suspended in dry methylene chloride (5 mL) then added were 5-tert-butyldimethylsilyloxy-2-(phthalimido)aniline (314 mg, 0.85 mmol)(see Example 167, step C, above) as a solution in 5 mL methylene chloride and 1 mL pyridine in several portions. The cloudy mixture was stirred 45 min then passed through a 35×80 mm plug of silica gel eluting first with methylene chloride then with 9:1:0.1 methylene chloride/methanol/-ammonium hydroxide. Appropriate fractions were combined, concentrated in vacuo and dried under vacuum to yield 360 mg (76%) of the desired intermediate phthalimide.

Workup

  1. temperatureunder reflux for 2 h
  2. temperatureto cool
  3. concentrationconcentrated in vacuo to a white foam
  4. customdried under vacuum
  5. additionthen added
  6. concentrationconcentrated in vacuo
  7. customdried under vacuum

Sources & evidence

ORD record
ord-efc384699eb9427fa77d88798da9aa23
Source dataset
uspto-grants-2001_11
Patent number
US06313122B1

Reaction notes

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