p-Toluenesulfonic acid monohydrate → HCID 67065996, compound

HRID 2093146Notes

Reaction equation

HRID 2093146 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[F:23])(O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH2:1]([N:8]1[CH2:9][CH:10]=[C:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[F:23])[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrate2×HCID 670660104-(2-Fluoro-4-methoxyphenyl)-1-(phenylmethyl)-4-piperidinol

Product 1

HCID 67065996HCID 67065996, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
80 °C

Procedure

A stirred mixture of 1-benzyl-4-(2-fluoro-4-methoxyphenyl)piperidin-4-ol (Step A; 300 mg; 0.952 mmol) and p-toluenesulfonic acid monohydrate (18 mg; 0.0952 mmol) in benzene (20 mL) was heated at 80° C. for 14 h. An additional 100 mg of p-toluenesulfonic acid monohydrate was added and the reaction heated at 80° C. for 1 h. The reaction was partitioned between EtOAc (50 mL) and H2O (50 mL). The aqueous layer was extracted with EtOAc (3×50 mL) and the combined extracts were washed with H2O (3×50 mL) and brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-10% EtOAc/hexanes gradient) to afford 1-benzyl-4-(2-fluoro-4-methoxyphenyl)1,2,3,6-tetrahydropyridine as a yellow oil. LCMS=297.9 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 9.56 (br s, 1 H), 7.42-7.38 (m, 2 H), 7.34 (t, J=7.3 Hz, 2 H), 7.28 (d, J=7.3 Hz, 1 H), 7.17 (t, J=8.7 Hz, 1 H), 6.64 (dd, J=8.7, 2.5 Hz, 1 H), 6.59 (dd, J=13.0, 2.5 Hz, 1 H), 5.91-5.89 (m, 1 H), 3.78 (s, 3 H), 3.66 (br s, 2 H), 3.18 (br s, 2 H), 2.71 (br s, 2 H), 2.54 (br s, 2 H).

Workup

  1. temperaturethe reaction heated at 80° C. for 1 h
  2. customThe reaction was partitioned between EtOAc (50 mL) and H2O (50 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  4. washthe combined extracts were washed with H2O (3×50 mL) and brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash silica gel chromatography (0-10% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-21d2c9a02b294d519cf62f6b4e84775a
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

Loading…