Isopropylamine → Esatenolol

HRID 1107057Notes

Reaction equation

HRID 1107057 reaction equation
[C:1]([CH2:4][C:5]1[CH:15]=[CH:14][C:8]([O:9][CH2:10][CH:11]2[O:13][CH2:12]2)=[CH:7][CH:6]=1)(=[O:3])[NH2:2].[CH:16]([NH2:19])([CH3:18])[CH3:17]>CO>[CH3:17][CH:16]([NH:19][CH2:12][C@H:11]([OH:13])[CH2:10][O:9][C:8]1[CH:14]=[CH:15][C:5]([CH2:4][C:1]([NH2:2])=[O:3])=[CH:6][CH:7]=1)[CH3:18]

Participants

4

Reactant 2

HCID 6363IsopropylamineHCID 1198572-(4-(2,3-Epoxypropoxy)phenyl)acetamide

Product 1

HCID 175540EsatenololYield 70.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
10 °C

Procedure

P-Hydroxyphenylacetamide (1 g) and (S)-glycidyl p-toluenesulfonate (1.51 g, 99.3% e.e.) were dissolved in acetone (30 ml). Potassium carbonate (1.19 g) was added to the solution and stirred for 30 hours under refluxing. After the reaction, inorganic materials were filtered off and acetone was removed to give 1.43 g of crude (S)-1-[p-(carbamoylmethyl)phenoxy-2,3-epoxypropane. Then, crude (S)-1-[p-(carbamoylmethyl)phenoxy-2,3-epoxypropane (1.43 g) was dissolved in methanol (8 ml). The solution was dropped in isopropylamine (6.8 g) under cooling to 10° C. over a period of 1 hour and the reaction temperature was raised to room temperature and stirred for 7 hours. After the reaction, the mixture was condensed in vacuo until crystals beginning to separate, cooled, filtrated by suction and dried in vacuo to give crude (S)-atenolol (1.29 g). The optical purity of it was 62.8% e.e. by measurement of Chiral column OD (Daisel Chemical industries Ltd.).

Workup

  1. temperaturethe reaction temperature was raised to room temperature
  2. customAfter the reaction
  3. customcondensed in vacuo until crystals
  4. customto separate
  5. temperaturecooled
  6. filtrationfiltrated by suction
  7. customdried in vacuo

Sources & evidence

ORD record
ord-8489f136fb044bed8b4bbc3ff88869ab
Source dataset
uspto-grants-2000_05
Patent number
US06057476

Reaction notes

Loading…