Hydrochloric Acid → Esatenolol
Reaction equation
[CH:1]1[C:6]([CH2:7][C:8]([NH2:10])=[O:9])=[CH:5][CH:4]=[C:3]([OH:11])[CH:2]=1.[OH-].[Na+].[CH2:14]([CH:16]1[O:18][CH2:17]1)Cl.Cl.[CH:20]([NH2:23])([CH3:22])[CH3:21]>O>[CH3:21][CH:20]([NH:23][CH2:14][C@H:16]([OH:18])[CH2:17][O:11][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][C:8]([NH2:10])=[O:9])=[CH:1][CH:2]=1)[CH3:22]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 5 °C
Procedure
p-Hydroxyphenylacetamide (30.02 g) was dissolved in 106.5 g of water containing sodium hydroxide (9.6 g) and the solution was cooled to 5° C. Epichlorohydrin (18.5 g, 98.9% e.e.) was dropped in the solution over a period of 10 minutes and the mixture was stirred for 24 hours at the same temperature. After confirmation of the progress of the reaction being 98% by HPLC, the reaction mixture was neutralized with 0.1 N hydrochloric acid at the same temperature and then dropped in isopropylamine (240 g) under cooling to 10° C. over a period of 1 hour and the reaction temperature was raised to room temperature and stirred for 3.5 hours. After the reaction, the reaction mixture was condensed in vacuo until crystals beginning to separate, cooled and filtrated by suction and dried in vacuo to give crude (S)-atenolol (51.26 g). The optical purity of it was 91.2% e.e. by measurement of Chiral column OD (Daisel Chemical Industries Ltd.).
Workup
- temperatureunder cooling to 10° C. over a period of 1 hour
- temperaturethe reaction temperature was raised to room temperature
- stirringstirred for 3.5 hours
- customAfter the reaction
- customcondensed in vacuo until crystals
- customto separate
- temperaturecooled
- filtrationfiltrated by suction
- customdried in vacuo
Sources & evidence
- ORD record
- ord-c68b8ec297af4fa6890c84177d871189
- Source dataset
- uspto-grants-2000_05
- Patent number
- US06057476
Reaction notes
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