Hydrochloric Acid → HCID 68644282, compound

HRID 1159562Notes

Reaction equation

HRID 1159562 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.C(N(CC)[C:16](=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=1[CH3:24])C.[CH3:28][O:29][CH2:30][C@H:31]1[CH2:35][CH2:34][CH2:33][N:32]1[CH2:36][CH2:37][C:38](N(OC)C)=[O:39].Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.CCCCCC.O>[CH3:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]2[C:18]=1[CH:24]=[C:38]([CH2:37][CH2:36][N:32]1[CH2:33][CH2:34][CH2:35][C@@H:31]1[CH2:30][O:29][CH3:28])[O:39][C:16]2=[O:25]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 11430Potassium CarbonateHCID 15621069N,N-Diethyl-2,3-dimethylbenzamideHCID 86613522HCID 86613522, compoundHCID 178418339Butyllithium

Product 1

HCID 68644282HCID 68644282, compoundYield 75.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Diisopropylamine (3.03 g) was dissolved in tetrahydrofuran (30 mL) and a solution (1.58 mol/L, 17.7 mL) of n-butyllithium in n-hexane was added dropwise under a nitrogen stream at −78° C. Subsequently, a solution of N,N-diethyl-2,3-dimethylbenzamide (3.28 g) in tetrahydrofuran was added dropwise. After the completion of the dropwise addition, the mixture was stirred at −78° C. for 1 hr. A solution of (R)-3-(2-methoxymethylpyrrolidin-1-yl)-N-methoxy-N-methylpropanamide (3.22 g) in tetrahydrofuran was added dropwise and the mixture was stirred at −78° C. for 30 min. After the completion of the reaction, concentrated hydrochloric acid (15 mL) and water (30 mL) were added and the mixture was heated under reflux. Tetrahydrofuran and hexane were evaporated and the mixture was further heated under reflux for 6 hr. After the completion of the reaction, the reaction mixture was cooled to room temperature and basified by adding potassium carbonate. The mixture was extracted with chloroform and dried over magnesium sulfate. The solvent was concentrated and the obtained residue was purified by silica gel column chromatography. The fraction eluted with chloroform:methanol=50:1 was concentrated to give (R)-5-methyl-3-[2-(2-methoxymethylpyrrolidin-1-yl)ethyl]isocoumarin (3.2 g).

Workup

  1. additionAfter the completion of the dropwise addition
  2. stirringthe mixture was stirred at −78° C. for 30 min
  3. additionwere added
  4. temperaturethe mixture was heated
  5. temperatureunder reflux
  6. customTetrahydrofuran and hexane were evaporated
  7. temperaturethe mixture was further heated
  8. temperatureunder reflux for 6 hr
  9. customAfter the completion of the reaction
  10. temperaturethe reaction mixture was cooled to room temperature
  11. extractionThe mixture was extracted with chloroform
  12. dry with materialdried over magnesium sulfate
  13. concentrationThe solvent was concentrated
  14. customthe obtained residue was purified by silica gel column chromatography
  15. washThe fraction eluted with chloroform
  16. concentrationmethanol=50:1 was concentrated

Sources & evidence

ORD record
ord-b9bf49aaf43548c28f0f8ac688c198d7
Source dataset
uspto-grants-2010_10
Patent number
US07812178B2

Reaction notes

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