Water → HCID 86612722, compound

HRID 1160483Notes

Reaction equation

HRID 1160483 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][CH2:7][C@H:8](O)[CH2:9][O:10][C:11]2[CH:12]=[C:13]([CH2:17][C@H:18]([O:24][CH:25]([CH3:27])[CH3:26])[C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:14]=[CH:15][CH:16]=2)=[C:4]([C:31]#[N:32])[CH:3]=1.C(N(S(F)(F)[F:39])CC)C.O.[Cl-].[Na+]>ClCCl>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][CH2:7][C@@H:8]([F:39])[CH2:9][O:10][C:11]2[CH:12]=[C:13]([CH2:17][C@H:18]([O:24][CH:25]([CH3:27])[CH3:26])[C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:14]=[CH:15][CH:16]=2)=[C:4]([C:31]#[N:32])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5234Sodium ChlorideHCID 123472(Diethylamino)sulfur trifluorideHCID 59516429HCID 59516429, compound

Product 1

HCID 86612722HCID 86612722, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-68 °C

Procedure

65.3 g of ethyl (2S)-3-{3-[(2R)-3-(4-chloro-2-cyanophenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropionate was dissolved in 1.3L of dichloromethane, which was then cooled to −68° C. Then 54 mL of diethylaminosulfur trifluoride was added, followed by stirring at room temperature for 4 days. The reaction mixture was cooled with ice, to which water (1 L) and a saturated sodium chloride solution (1 L) were then added, followed by extraction with ethyl acetate (4 L). The organic layer was washed with the saturated sodium chloride solution (2 L) and dried with anhydrous magnesium sulfate, followed by distilling off the solvent under a reduced pressure. The residue was purified using silica gel column chromatography to obtain 33 g of ethyl (2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionate from a hexane-ethyl acetate (7:1→5:1)-eluted fraction. This compound was dissolved in 400 mL of ethanol, to which 107 mL of 2N sodium hydroxide aqueous solution was then added, followed by stirring the reaction mixture at room temperature for 2 hours. The reaction mixture was cooled with ice, to which water (500 mL) and a 5N hydrochloric acid aqueous solution (50 mL) were then added before further adding water (1 L), followed by extraction with ethyl acetate (2.5 L). The organic layer was washed with the saturated sodium chloride solution (1 L) and dried with anhydrous magnesium sulfate, followed by distilling off the solvent under a reduced pressure. The residue was purified using silica gel column chromatography to obtain 27.6 g of the title compound in the form of colorless oily matter from a hexane-ethyl acetate (3:1→1:1)-eluted fraction.

Workup

  1. extractionfollowed by extraction with ethyl acetate (4 L)
  2. washThe organic layer was washed with the saturated sodium chloride solution (2 L)
  3. dry with materialdried with anhydrous magnesium sulfate
  4. distillationby distilling off the solvent under a reduced pressure
  5. customThe residue was purified

Sources & evidence

ORD record
ord-186dbcfad7574152813e0bd77732a8b3
Source dataset
uspto-grants-2010_10
Patent number
US07816405B2

Reaction notes

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