Methanesulfonate → HCID 178516053, compound

HRID 896642Notes

Reaction equation

HRID 896642 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.S([O-])(=O)(=O)C>C1COCC1.CCOC(C)=O>[C:5]1([C:8]#[C:9][CH2:10][NH:1][C@H:2]2[CH2:3][CH2:4][C@H:5]([C:8]3[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=3)[CH2:6][CH2:7]2)[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1

Participants

5

Reactant 2

HCID 85257MethanesulfonateHCID 178511500HCID 178511500, compound

Product 1

HCID 178516053HCID 178516053, compoundYield 58.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of trans-4-(4-hydroxyphenyl)cyclohexylamine 5 (0.35 g, 1.8 mmol) and mesylate 7 (0.32 g, 1.5 mmol) in THF (15 mL) was refluxed under N2 for 17 hours. The reaction mixture was diluted with EtOAc (40 mL) and washed with H2O, then saturated NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 99:1 CHCl3:MeOH to 97:3 CHCl3:MeOH) and conversion to the maleate salt gave trans-4-[4-(3-phenylprop-2-ynylamino)cyclohexyl]phenol (160 mg, 26%) as a white solid: mp 171-179° C.; IR (KBr): 2938, 1700, 1516cm−1; 1H NMR (300 MHz, CD3OD) δ 7.52-7.35 (m, 5H), 7.04 (d, J=8 Hz, 2H), 6.69 (d, J=8 Hz, 2H), 6.25 (s, 2H), 4.21 (s, 2H), 3.45-3.35 (obs m, 1H) 2.52-2.42 (m, 1H), 2.31-2.20 (m, 2H), 2.05-1.60 (m, 2H), 1.67-1.48 (m, 4H); CI-MS (methane) (m/z): 306 [M+H]+; HPLC: method A, 7.63 minutes (97.9%); method B, 14.01 minutes (97.6%); Anal. Calcd for C21H23NO.C4H4O4: C, 71.24; H, 6.46; N, 3.32. Found: C, 71.21; H, 6.51; N, 3.22.

Workup

  1. temperaturewas refluxed under N2 for 17 hours
  2. washwashed with H2O
  3. dry with materialsaturated NaCl, dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography (silica, 99:1 CHCl3:MeOH to 97:3 CHCl3:MeOH) and conversion to the maleate salt

Sources & evidence

ORD record
ord-e881bf7b25c54c3698b567f699ec5e88
Source dataset
uspto-grants-2005_07
Patent number
US06919377B2

Reaction notes

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