Boric Acid → 2-Ethoxy-4-(3-((S)-3-methy-1-(2-piperidin-1-yl-phenyl)-butylamino)-2-oxo-propyl)-benzoic acid ethyl ester

HRID 423214Notes

Reaction equation

HRID 423214 reaction equation
[CH3:1][CH:2]([CH3:18])[CH2:3][C@H:4]([NH2:17])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.[CH2:19]([O:21][C:22]1[CH:23]=[C:24]([CH2:33][C:34](O)=[O:35])[CH:25]=[CH:26][C:27]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:20].B(O)(O)O>C1(C)C=CC=CC=1>[CH2:19]([O:21][C:22]1[CH:23]=[C:24]([CH2:33][C:34]([NH:17][C@H:4]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:3][CH:2]([CH3:18])[CH3:1])=[O:35])[CH:25]=[CH:26][C:27]=1[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:20]

Participants

5

Reactant 3

HCID 7628Boric AcidHCID 101312123-Ethoxy-4-ethoxycarbonylphenylacetic acidHCID 105146093-Methyl-1-(2-piperidinophenyl)-1-butylamine, (S)-

Product 1

HCID 106484192-Ethoxy-4-(3-((S)-3-methy-1-(2-piperidin-1-yl-phenyl)-butylamino)-2-oxo-propyl)-benzoic acid ethyl esterYield 73.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
27.5 °C

Procedure

In a round bottom flask fitted with a dean stark condenser, (S)-3-methyl-1-(2-piperidinophenyl)-1-butylamine (10 g, 0.0406 mol) was dissolved in toluene (100 ml), followed by the addition of 3-ethoxy-4-ethoxycarbonyl phenyl acetic acid (10.26 g, 0.0407 mol) and boric acid (0.26 g, 0.0042 mol). The reaction mixture was refluxed for 16-18 hours. The resulting mass was then cooled to 25-30° C. followed by filtration. The filtrate was washed with water and 1.0% sodium bicarbonate solution followed by complete distillation of toluene and the resulting residue was stirred with hexane (50 ml) for 1 hour. The precipitated solid was filtered and washed with hexane (10 ml). The wet product was dried at 50-55° C. under vacuum for 4-6 hours to produce Ethyl (S)-2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonyl methyl]-benzoate (Yield=73.3%; HPLC Purity: 99.50%).

Workup

  1. customIn a round bottom flask fitted with a dean stark condenser
  2. temperatureThe reaction mixture was refluxed for 16-18 hours
  3. filtrationfollowed by filtration
  4. washThe filtrate was washed with water and 1.0% sodium bicarbonate solution
  5. distillationfollowed by complete distillation of toluene
  6. filtrationThe precipitated solid was filtered
  7. washwashed with hexane (10 ml)
  8. customThe wet product was dried at 50-55° C. under vacuum for 4-6 hours

Sources & evidence

ORD record
ord-22778ac9720749c5aa3d48fdb7d40014
Source dataset
uspto-grants-2012_01
Patent number
US08101769B2

Reaction notes

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