Water → 1-Methyl-4-(benzo[b]thien-3-yl)-4-piperidinol

HRID 1283299Notes

Reaction equation

HRID 1283299 reaction equation
C([Li])CCC.Br[C:7]1[C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[S:10][CH:11]=1.[CH3:16][N:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1.O>C(OCC)C>[CH3:16][N:17]1[CH2:22][CH2:21][C:20]([C:7]2[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[S:10][CH:11]=2)([OH:23])[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 962WaterHCID 740491-Methyl-4-piperidoneHCID 123250Benzo(b)thiophene, 3-bromo-HCID 178418339Butyllithium

Product 1

HCID 215196901-Methyl-4-(benzo[b]thien-3-yl)-4-piperidinol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

13.5 g (0.21 mole) of n-butyllithium in 145 ml of absolute diethyl ether is precooled to -70° to -80°. To this solution there is then added dropwise within 30 minutes, at a temperature of -70°, a solution of 42.6 g of 3-bromobenzo[b]thiophene in 250 ml of absolute diethyl ether. The solution is thereupon stirred for a further 30 minutes at -70°. An addition is then made dropwise, in the course of 30 minutes, of a solution of 23.5 g of 1-methyl-4-piperidone in 100 ml of absolute diethyl ether; the reaction temperature is held by external cooling at -70°, and the reaction solution is subsequently stirred for a further 10 hours at -70°. The reaction solution is thereupon heated to -5°, and 300 ml of water is added dropwise. The organic phase is separated, and the aqueous phase is extracted twice with 400 ml of ethyl acetate. The organic phases are combined, dried with sodium sulphate, filtered off with suction and concentrated by evaporation. The residue is dissolved in 500 ml of 2N hydrochloric acid, and the acid solution is washed with ether. The aqueous solution is then adjusted be addition by 10% sodium hydroxide solution to have a pH-value of 12, and extracted with one litre of chloroform. The chloroform solution is dried with sodium sulphate, filtered off with suction and concentrated by evaporation to obtain crude 1-methyl-4-(benzo[b]thien-3-yl)-4-piperidinol. The free base melts at 150°-151° after recrystallisation from acetone.

Workup

  1. customis precooled to -70° to -80°
  2. additionTo this solution there is then added dropwise within 30 minutes, at a temperature of -70°
  3. additionAn addition
  4. temperatureby external cooling at -70°
  5. stirringthe reaction solution is subsequently stirred for a further 10 hours at -70°
  6. temperatureThe reaction solution is thereupon heated to -5°
  7. customThe organic phase is separated
  8. extractionthe aqueous phase is extracted twice with 400 ml of ethyl acetate
  9. dry with materialdried with sodium sulphate
  10. filtrationfiltered off with suction
  11. concentrationconcentrated by evaporation
  12. dissolutionThe residue is dissolved in 500 ml of 2N hydrochloric acid
  13. washthe acid solution is washed with ether
  14. additionaddition by 10% sodium hydroxide solution
  15. extractionextracted with one litre of chloroform
  16. dry with materialThe chloroform solution is dried with sodium sulphate
  17. filtrationfiltered off with suction
  18. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-91057363583f46ffb166228f83db41c4
Source dataset
uspto-grants-1976_08
Patent number
US03974280

Reaction notes

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