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

HRID 423215Notes

Reaction equation

HRID 423215 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH2:15][C:16]([OH:18])=O)[CH:7]=[CH:8][C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH3:2].C1(B(O)O)C=CC=CC=1.[CH3:28][CH:29]([CH3:45])[CH2:30][C@H:31]([NH2:44])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH2:15][C:16]([NH:44][C@H:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[N:38]2[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]2)[CH2:30][CH:29]([CH3:45])[CH3:28])=[O:18])[CH:7]=[CH:8][C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH3:2]

Participants

5

Reactant 3

HCID 66827Phenylboronic 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 89.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
27.5 °C

Procedure

In a round bottom flask fitted with a dean stark condenser, 3-Ethoxy-4-ethoxycarbonyl phenyl acetic acid (10.26 g, 0.0426 mol) was dissolved in toluene (100 ml) followed by slow addition of phenylboronic acid (0.494 g, 0.0040 mol) and (S)-3-methyl-1-(2-piperidinophenyl)-1-butylamine (10 g, 0.0406 mol). The reaction mixture was refluxed for 16-18 hours. The resulting mass was cooled at 25-30° C. followed by filtration. The toluene layer was washed with water and 1% sodium bicarbonate solution followed by complete distillation of toluene. Hexane (50 ml) was added to the resulting residue after complete removal of toluene in order to precipitate the solid, with stirring for 1 hour. The resulting solid was filtered and washed with hexane (10 ml). The wet material was further 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)-aminocarbonylmethyl]benzoate (Yield=89.6%; HPLC Purity: 99.66%).

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 toluene layer was washed with water and 1% sodium bicarbonate solution
  5. distillationfollowed by complete distillation of toluene
  6. additionHexane (50 ml) was added to the resulting residue
  7. customafter complete removal of toluene in order
  8. customto precipitate the solid
  9. filtrationThe resulting solid was filtered
  10. washwashed with hexane (10 ml)
  11. customThe wet material was further dried at 50-55° C. under vacuum for 4-6 hours

Sources & evidence

ORD record
ord-be53759529944a97bf1128ee3b61021a
Source dataset
uspto-grants-2012_01
Patent number
US08101769B2

Reaction notes

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