Calcium diethanolate → E-3030 trihydrate

HRID 1160484Notes

Reaction equation

HRID 1160484 reaction equation
[O-:1]CC.[O-:4]CC.[Ca+2:7].[Cl:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][C@@H:15]([F:33])[CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH2:24][C@H:25]([O:29][CH:30]([CH3:32])[CH3:31])[C:26]([OH:28])=[O:27])[CH:21]=[CH:22][CH:23]=2)=[C:11]([C:36]#[N:37])[CH:10]=1>CO>[OH2:1].[OH2:4].[OH2:13].[Cl:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][C@@H:15]([F:33])[CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH2:24][C@H:25]([O:29][CH:30]([CH3:32])[CH3:31])[C:26]([O-:28])=[O:27])[CH:21]=[CH:22][CH:23]=2)=[C:11]([C:36]#[N:37])[CH:10]=1.[Cl:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][C@@H:15]([F:33])[CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH2:24][C@H:25]([O:29][CH:30]([CH3:32])[CH3:31])[C:26]([O-:28])=[O:27])[CH:21]=[CH:22][CH:23]=2)=[C:11]([C:36]#[N:37])[CH:10]=1.[Ca+2:7]

Participants

4

Reactant 2

HCID 6451473Calcium diethanolateHCID 11949482Benzenepropanoic acid, 3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]-α-(1-methylethoxy)-, (αS)-

Product 1

HCID 25033287E-3030 trihydrateYield 141%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

4.6 g of calcium diethoxide was dissolved in 500 mL of methanol, to which a methanol (300 mL) solution of 30.8 g of (2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionic acid was then added, followed by stirring the reaction mixture overnight at room temperature. Insoluble matter in the reaction mixture was filtered, and the solvent was distilled off under a reduced pressure. To the residue were added 250 mL of methanol and 60 mL of water, followed by heating the reaction mixture to reflux. The reaction mixture was then cooled, followed by filtering the precipitated solid to obtain 32 g of the title compound as a crude product. To this compound was added 1.5 L of ethanol, and the reaction mixture was heated to reflux. Insoluble matter was hot-filtered, and the solution was again heated to reflux. To the reaction mixture was added 20 ml of water to slowly cool the mixture, and the reaction mixture was stirred overnight at room temperature. The precipitated solid was filtered, washed with ethanol:water=9:1, and subjected to forced-air drying at 40° C. for 18 hours. There was obtained 29 g of the title compound in the form of white crystal. The 1H-NMR data thereof coincided with that of the compound of Example 1-(15).

Workup

  1. additionwas then added
  2. filtrationInsoluble matter in the reaction mixture was filtered
  3. distillationthe solvent was distilled off under a reduced pressure
  4. additionTo the residue were added 250 mL of methanol and 60 mL of water
  5. temperatureby heating the reaction mixture
  6. temperatureto reflux
  7. temperatureThe reaction mixture was then cooled
  8. filtrationby filtering the precipitated solid

Sources & evidence

ORD record
ord-62f28186de4a401f8c95649683efdd40
Source dataset
uspto-grants-2010_10
Patent number
US07816405B2

Reaction notes

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