Acetic Acid → HCID 9925417, compound

HRID 896647Notes

Reaction equation

HRID 896647 reaction equation
CC(O)=O.OS(O)(=O)=O.[CH2:10]([N:12]([CH2:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH:13]1[CH2:18][CH2:17][CH:16]([C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)[CH2:15][CH2:14]1)[CH3:11].ClC[C:37]([NH:39]CO)=O>O>[NH2:39][CH2:37][C:21]1[CH:20]=[C:19]([CH:16]2[CH2:17][CH2:18][CH:13]([N:12]([CH2:10][CH3:11])[CH2:26][CH2:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:14][CH2:15]2)[CH:24]=[CH:23][C:22]=1[OH:25]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 62466N-Methylol-alpha-chloroacetamideHCID 9905840HCID 9905840, compound

Product 1

HCID 9925417HCID 9925417, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

A mixture of HOAc and H2SO4 (1 mL, 9:1, v:v) was cooled to 10° C. 4-{4-[ethyl(3-phenylpropyl)amino]cyclohexyl}phenol (200 mg, 0.53 mmol) and 2-chloro-N-(hydroxymethyl)acetamide (66 mg, 0.53 mmol) were added portionwise. The reaction mixture was warmed to room temperature and stirred for 16 hours. The mixture was poured onto ice (1 g) and water (10 mL) was added. After concentration under reduced pressure, a mixture of EtOH and HCl (6.5 mL, 10:3, v:v) was added, and the mixture was heated under reflux for 1.5 hours. The mixture was cooled to room temperature and concentrated under reduced pressure. Purification by flash chromatography (silica, 90:10:0.5 CH2Cl2:MeOH:NH4OH), followed by formation of the HCl salt, gave 2-aminomethyl-4-{4-[ethyl(3-phenylpropyl)amino]cyclohexyl}phenol (65 mg, 28%), as a yellow solid: mp 168-173° C.; IR (KBr): 2940, 1510, 1453 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 10.16 (br s, 1H), 9.96 (s, 1H), 8.1 (br s, 2H), 7.35-7.17 (m, 6H), 7.06 (dd, J=8 Hz, 1H), 6.85 (d, J=8 Hz, 1H), 3.90 (br d, J=5 Hz, 2H), 3.45-2.98 (m, 4H), 2.71-2.65 (m, 2H), 2.52-2.39 (m, 2M), 2.19-2.10 (m, 2H), 2.10-2.05 (m, 2H), 1.90-1.83 (m, 2H), 1.70-1.49 (m, 4H), 1.27 (t, J=7 Hz, 3H) API-MS (methane) (m/z): 367 [M+H]+; HRMS-API (m/z): [M+H]+ Calcd for C24H34N2O, 367.2749. found: 367.2741. Anal. Calcd for C24H34N2O.02HCl.H2O: C, 64.93; H, 8.29; N, 6.31. Found: C, 64.90; H, 8.53; N, 6.09.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. additionwas added
  3. concentrationAfter concentration under reduced pressure
  4. additiona mixture of EtOH and HCl (6.5 mL, 10:3, v:v)
  5. additionwas added
  6. temperaturethe mixture was heated
  7. temperatureunder reflux for 1.5 hours
  8. temperatureThe mixture was cooled to room temperature
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash chromatography (silica, 90:10:0.5 CH2Cl2:MeOH:NH4OH)

Sources & evidence

ORD record
ord-23a12f6dff86469b972b05e75539b30b
Source dataset
uspto-grants-2005_07
Patent number
US06919377B2

Reaction notes

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