Benzothiazole → [2-Benzothiazolyl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl)methanone

HRID 1450440

Reaction equation

HRID 1450440 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C([Li])CCC.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][CH:28]([C:31](OC)=[O:32])[CH2:27][CH2:26]2)=[CH:19][CH:18]=1>O1CCCC1.CCCCCC>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:31]([CH:28]1[CH2:29][CH2:30][N:25]([CH2:24][CH2:23][C:20]2[CH:21]=[CH:22][C:17]([O:16][CH3:15])=[CH:18][CH:19]=2)[CH2:26][CH2:27]1)=[O:32]

Participants

6

Reactant 3

HCID 7222BenzothiazoleHCID 108695871-[2-(4-Methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl esterHCID 178418339Butyllithium

Product 1

HCID 9842862[2-Benzothiazolyl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl)methanone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve freshly distilled benzothiazole (3.41 g, 25.24 mmol) in anhydrous tetrahydrofuran (60 mL), place under an argon atmosphere and cool to -78° C. Add, by dropwise addition, n-butyllithium (15.14 mL of a 2.5M solution in hexane, 37.86 mmol) and stir briefly at -78° C. Add, by dropwise addition, a solution of 1-[2-(4-methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl ester (7.0 g, 25.24 mmol) in anhydrous tetrahydrofuran (40 mL). Stir for 1 hour at -78° C., quench with methanol (5 mL) and pour into saturated ammonium chloride (100 mL). Filter, separate the organic phase and extract the aqueous phase with ethyl acetate. Combine the organic phases and wash with water and brine. Dry (MgSO4) and evaporate the solvent in vacuo. Purify by chromatography (ethyl acetate) and recrystallize (cyclohexane) to give the title compound as a pale yellow powder; mp 118°-120° C.

Workup

  1. additionAdd, by dropwise addition
  2. stirringStir for 1 hour at -78° C.
  3. customquench with methanol (5 mL)
  4. additionpour into saturated ammonium chloride (100 mL)
  5. filtrationFilter
  6. customseparate the organic phase
  7. extractionextract the aqueous phase with ethyl acetate
  8. washwash with water and brine
  9. dry with materialDry (MgSO4)
  10. customevaporate the solvent in vacuo
  11. customPurify by chromatography (ethyl acetate)
  12. customrecrystallize (cyclohexane)

Sources & evidence

ORD record
ord-1602ea0c7c6341799c4f3bf9d9dcc4b8
Source dataset
uspto-grants-1997_02
Patent number
US05602147

Linked notes

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