p-Toluenesulfonic acid → HCID 58852367, compound

HRID 970726Notes

Reaction equation

HRID 970726 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:9]2(O)[CH2:14][CH2:13][CH:12]([N:15]([CH3:17])[CH3:16])[CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:14][CH2:13][CH:12]([N:15]([CH3:17])[CH3:16])[CH2:11][CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 69351008HCID 69351008, compound

Product 1

HCID 58852367HCID 58852367, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Combine 1-(3-bromo-5-fluoro-phenyl)-4-dimethylamino-cyclohexanol (14.5 g, 45.9 mmol), p-TsOH (21.8 g, 114.6 mmol) and toluene (200 mL) and heat to reflux for 3 hr. Cool to ambient temperature and partition between ethyl acetate (500 mL) and 1M NaOH solution (250 mL). Wash the organic layer with 1M NaOH solution (200 mL) and saturated aqueous NaCl (200 mL), dry over sodium sulfate, filter and concentrate. Purify the residue by chromatography (silica gel, 10% 2M NH3/MeOH in DCM) to obtain (4-(3-bromo-5-fluoro-phenyl)-cyclohex-3-enyl)-dimethyl-amine (10.8 g, 79%): MS (ES) m/z=298 (M−H)−, 300 (M+H)+; 1H NMR (CDCl3): δ 7.25 (d, 1H, J=2 Hz), 7.02 (dd, 1H, J=8 Hz, J=2 Hz), 6.9 (dd, 1H, J=8 Hz, J=2 Hz), 6.04 (m, 1H), 2.38 (m, 4H), 2.27 (s, 6H), 2.09 (m, 2H), 1.48 (m, 1H).

Workup

  1. temperatureto reflux for 3 hr
  2. custompartition between ethyl acetate (500 mL) and 1M NaOH solution (250 mL)
  3. washWash the organic layer with 1M NaOH solution (200 mL) and saturated aqueous NaCl (200 mL)
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the residue by chromatography (silica gel, 10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-2830d036d4c443c892ff9a3a78c93bc1
Source dataset
uspto-grants-2007_12
Patent number
US07312236B2

Reaction notes

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