Acetic Acid → HCID 14502048, compound

HRID 231860Notes

Reaction equation

HRID 231860 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1.[CH2:13]([N:15]([CH2:29][CH3:30])[CH2:16][CH2:17][N:18]1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28])[CH3:14].C(O)(=O)C>CCCCCC.O1CCCC1.C(N(CC)CC)C.C(OCC)(=O)C>[CH2:29]([N:15]([CH2:13][CH3:14])[CH2:16][CH2:17][N:18]1[C:22]([OH:23])([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)[C:21]2[C:20](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:19]1=[O:28])[CH3:30]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 122863-BromopyridineHCID 437251HCID 437251, compoundHCID 178418339Butyllithium

Product 1

HCID 14502048HCID 14502048, compoundYield 52.2%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 0.11 mole of butyl lithium in 68 ml of hexane and 150 ml of tetrahydrofuran was added a solution of 15.80 g of 3-bromopyridine in 20 ml of tetrahydrofuran at -78° C. After stirring for 30 minutes at -78° C., a solution of 24.63 g of N-(2-diethylaminoethyl)phthalimide in 30 ml of tetrahydrofuran was added to the mixture. After stirring at -78° C. for 1 hour, a solution of 6.61 g of acetic acid in 30 ml of tetrahydrofuran was added, and the mixture was concentrated under reduced pressure. To the residue were added 300 ml of water and 300 ml of ethyl ether, and pH of the mixture was adjusted to 1.5 with 4N-hydrochloric acid. After shaking, the organic layer was discarded and 200 ml of methylene chloride was added to the aqueous layer. The pH was adjusted to 10 with 10N-sodium hydroxide solution. After shaking, the aqueous layer was discarded and the organic layer was washed with saturated aqueous sodium chloride solution. After drying over anhydrous sodium sulfate, the organic layer was concentrated under reduced pressure. The crude product obtained was subjected to silica gel column chromatography (ethyl acetate:triethylamine=20:1). A major fraction was concentrated under reduced pressure to give 16.99 g of 2-(2 -diethylaminoethyl)-3-hydroxy-3-(3-pyridyl)isoindolin-1-one (Compound 21).

Workup

  1. stirringAfter stirring at -78° C. for 1 hour
  2. concentrationthe mixture was concentrated under reduced pressure
  3. additionTo the residue were added 300 ml of water and 300 ml of ethyl ether, and pH of the mixture
  4. stirringAfter shaking
  5. addition200 ml of methylene chloride was added to the aqueous layer
  6. stirringAfter shaking
  7. washthe organic layer was washed with saturated aqueous sodium chloride solution
  8. dry with materialAfter drying over anhydrous sodium sulfate
  9. concentrationthe organic layer was concentrated under reduced pressure
  10. customThe crude product obtained
  11. concentrationA major fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a4d9df7e27bd41f0b644c2213f08d201
Source dataset
uspto-grants-1989_07
Patent number
US04849441

Reaction notes

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