3-Methylbenzo[b]thiophene → HCID 12992766, compound

HRID 1837479Notes

Reaction equation

HRID 1837479 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[S:4][CH:3]=1.C([Li])CCC.[CH2:16]([N:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)[CH:17]=[CH2:18]>O1CCCC1.[Cl-].[Na+].O>[OH:25][C:22]1([C:3]2[S:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:2]=2[CH3:1])[CH2:23][CH2:24][N:19]([CH2:16][CH:17]=[CH2:18])[CH2:20][CH2:21]1

Participants

6

Reactant 3

HCID 738173-Methylbenzo[b]thiopheneHCID 113440581-(Prop-2-en-1-yl)piperidin-4-oneHCID 178418339Butyllithium

Product 1

HCID 12992766HCID 12992766, compoundYield 83.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Scheme IA, step A: To a solution of 3-methylbenzothiophene (2.863 g, 19.3 mmol) in tetrahydrofuran (80 mL) at −78° C. was added a solution of n-butyllithium (13.3 mL, 21.2 mmol, 1.6 M in hexanes). The solution was warmed to 0° C. for one hour then recooled to −78° C. A solution of 1-(2-propenyl)-4-piperidone (2.957 g, 21.2 mmol) in tetrahydrofuran was added dropwise and the mixture was warmed to 20° C. After stirring for 18 hours at 20° C. the mixture was diluted with brine and extracted 3 times with ethyl acetate. The combined organics were dried over sodium sulfate then filtered and evaporated. The residue was purified using silica gel chromatography (dichloromethane/5% methanol in dichloromethane gradient eluent) to give 4.61 g (83%) of the intermediate title compound as a white amorphous solid. FDMS m/e=288 (M++1).

Workup

  1. customthen recooled to −78° C
  2. temperaturethe mixture was warmed to 20° C
  3. extractionextracted 3 times with ethyl acetate
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. filtrationthen filtered
  6. customevaporated
  7. customThe residue was purified

Sources & evidence

ORD record
ord-1071cfcb1efc48f3bebba1cec73e6ec9
Source dataset
uspto-grants-2004_08
Patent number
US06784180B2

Reaction notes

Loading…