Sodium Iodide → Esatenolol

HRID 1107053Notes

Reaction equation

HRID 1107053 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.[F-].[Cs+].[I-].[Na+].[CH2:16]([C@@H:18]1[O:20][CH2:19]1)Cl.[CH:21]([NH2:24])([CH3:23])[CH3:22]>CN(C=O)C>[CH3:22][CH:21]([NH:24][CH2:16][C@H:18]([OH:20])[CH2:19][O:11][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][C:8]([NH2:10])=[O:9])=[CH:1][CH:2]=1)[CH3:23]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 6363IsopropylamineHCID 25953Cesium fluorideHCID 86986(4-Hydroxyphenyl)acetamideHCID 2734062(-)-Epichlorohydrin

Product 1

HCID 175540EsatenololYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

p-Hydroxyphenylacetamide (1 g) was dissolved in DMF (5 ml) under nitrogen atmosphere and the solution was cooled to 0° C. Cesium fluoride (3.02 g) and sodium iodide (0.1 g) were added thereto and the mixture was stirred for 1 hour. Then (R)-epichlorohydrin (0.62 g, 98.4% e.e.) was added thereto and the mixture was stirred for 30 hours at the same temperature. After the reaction, the reaction mixture was dropped over a period of one hour in isopropylamine (9 g) previously cooled to 10° C. The temperature of the solution was raised to room temperature and stirred for 12 hours. Then the product was treated in the same manner as Example 1 to give 1.53 g of (S)-atenolol (yield 87%, optical purity 98.3% e.e.) as colorless crystals.

Workup

  1. stirringthe mixture was stirred for 30 hours at the same temperature
  2. customAfter the reaction
  3. temperaturepreviously cooled to 10° C
  4. temperatureThe temperature of the solution was raised to room temperature
  5. stirringstirred for 12 hours
  6. additionThen the product was treated in the same manner as Example 1

Sources & evidence

ORD record
ord-685b4a3cf6504058be4d83080647dd21
Source dataset
uspto-grants-2000_05
Patent number
US06057476

Reaction notes

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