Hydrochloric Acid → (1-Methyl-2-piperidinyl)methyl 1H-indole-3-carboxylate

HRID 893274Notes

Reaction equation

HRID 893274 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH2:8][OH:9].[Li]CCCC.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[C:16]1C(Cl)=O.Cl.C1C[O:31][CH2:30]C1>CCCCCC>[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([C:30]([O:9][CH2:8][CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][N:2]2[CH3:1])=[O:31])=[CH:16]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 893941-Methyl-2-piperidinemethanolHCID 118162081H-indole-2-carbonyl ChlorideHCID 178418339Butyllithium

Product 1

HCID 19891949(1-Methyl-2-piperidinyl)methyl 1H-indole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To a THF solution (17 ml) of 1-methyl-2-piperidinemethanol (1.70 g, 13.2 mmol) cooled in an ice-sodium chloride bath to -5° C. was dropwise added a 1.5M hexane solution of n-BuLi (8.7 ml, 13.0 mmol) over a period of 5 min. Stirring was continued under ice-cooling for 30 min. To a mixture was then dropwise added a THF solution (5 ml) of indolecarboxylic acid chloride (1.50 g, 8.35 mmol) over a period of 5 min. After stirring at room temperature for 5 hours, a reaction solution was poured onto diluted hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were then adjusted with saturated aqueous NaCO3 to a pH of >10 and again extracted with EtOAc. The basic extract was washed successively with water and saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The pale yellow crystals thus produced were recrystallized from a chloroform-methanol mixture to give 1.20 g of the title compound as prisms. m.p. 168°-170° C.;

Workup

  1. temperaturecooling for 30 min
  2. stirringAfter stirring at room temperature for 5 hours
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. extractionagain extracted with EtOAc
  6. extractionThe basic extract
  7. washwas washed successively with water and saturated aqueous sodium chloride
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe pale yellow crystals thus produced
  11. customwere recrystallized from a chloroform-methanol mixture

Sources & evidence

ORD record
ord-fbb7656bd37a41eca1fe131aff3f924f
Source dataset
uspto-grants-1992_06
Patent number
US05124324

Reaction notes

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