Potassium Hydroxide → HCID 11085430, compound

HRID 840423Notes

Reaction equation

HRID 840423 reaction equation
Br.[NH+]1C=CC=CC=1.C[O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[C:12]([S:22][CH3:23])[CH:11]=1.[OH-].[K+]>O.CCO>[OH:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]2)=[C:12]([S:22][CH3:23])[CH:11]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 10933529HCID 10933529, compoundHCID 21226041Pyridinium hydrobromide

Product 1

HCID 11085430HCID 11085430, compoundYield 104.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
225 °C

Procedure

A mixture of pyridinium hydrobromide (20.76 g) and 4-[4-methoxy-2-methylthiophenyl]piperidine (6.16 g) was heated at 225° C. for 18 h. The reaction mixture was cooled, dissolved in 200 mL H2O, adjusted to pH 7 with 1N KOH, and extracted with hexane (4×50 mL). The aqueous layer was concentrated under reduced pressure to give an oil which was dissolved in 200 mL EtOH and stirred for 0.5 h. The precipitate was filtered and washed with EtOH (2×40 mL). The filtrate and all washes were combined and concentrated under reduced pressure. The crude product was purified by chromatography (9:1 DCM:MeOH) to give 6.06 g of 4-[4-hydroxy-2-methylthiophenyl]piperidine as the hydrobromide salt. 1H NMR (DMSO d6) δ 9.44 (s, 1H), 8.49 (m, 2H), 6.97 (d, 1H), 6.66 (d, 1H), 6.58 (dd, 1H), 3.43-3.30 (dm, 2H), 3.13-2.95 (m, 3H), 2.42 (s, 3H), 1.91-1.61 (m, 4H); MS m/z 225 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with hexane (4×50 mL)
  3. concentrationThe aqueous layer was concentrated under reduced pressure
  4. customto give an oil which
  5. filtrationThe precipitate was filtered
  6. washwashed with EtOH (2×40 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by chromatography (9:1 DCM:MeOH)

Sources & evidence

ORD record
ord-6a0cad292e924c4091e34729111a6044
Source dataset
uspto-grants-2002_04
Patent number
US06365602B1

Reaction notes

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