Hydrochloric Acid → Benzenepropanoic acid, 3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]-α-(1-methylethoxy)-, (αS)-

HRID 1160478Notes

Reaction equation

HRID 1160478 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][CH2:7][C@@H:8]([F:27])[CH2:9][O:10][C:11]2[CH:12]=[C:13]([CH2:17][C@H:18]([O:23][CH:24]([CH3:26])[CH3:25])[C:19]([O:21]C)=[O:20])[CH:14]=[CH:15][CH:16]=2)=[C:4]([C:30]#[N:31])[CH:3]=1.C(OC)(C)(C)C.Cl>O1CCCC1.O.[OH-].[Na+]>[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][CH2:7][C@@H:8]([F:27])[CH2:9][O:10][C:11]2[CH:12]=[C:13]([CH2:17][C@H:18]([O:23][CH:24]([CH3:26])[CH3:25])[C:19]([OH:21])=[O:20])[CH:14]=[CH:15][CH:16]=2)=[C:4]([C:30]#[N:31])[CH:3]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 15413tert-Butyl methyl etherHCID 59516431HCID 59516431, compound

Product 1

HCID 11949482Benzenepropanoic acid, 3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]-α-(1-methylethoxy)-, (αS)-Yield 103.5%

Reagents, catalysts & solvents 3

HCID 14798Sodium HydroxideCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Methyl (2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionate (186 g, 0.41 mol) was suspended in tetrahydrofuran (928 mL) and water (928 mL), followed by adding dropwise a 2N NaOH aqueous solution (309 mL, 0.62 mmol) to the reaction mixture at room temperature and the mixture was stirred for 3.5 hours. Tert-butylmethyl ether (1,856 mL) and water (928 mL) were added to the reaction mixture to separate an aqueous layer. Tert-butylmetyl ether (1,856 mL) was added to the aqueous layer, followed by adding dropwise a 2N hydrochloric acid aqueous solution (371 mL, 0.74 mol) at room temperature to separate an organic layer. The organic layer was washed with water (928 mL) and then subjected to vacuum concentration to obtain 185 g of the title compound (yield: 90%).

Workup

  1. customto separate an aqueous layer
  2. additionTert-butylmetyl ether (1,856 mL) was added to the aqueous layer
  3. customto separate an organic layer
  4. washThe organic layer was washed with water (928 mL)
  5. concentrationsubjected to vacuum concentration

Sources & evidence

ORD record
ord-b55a3da2a7c646d0923bd318b0054cc4
Source dataset
uspto-grants-2010_10
Patent number
US07816405B2

Reaction notes

Loading…