Sodium Chloride → HCID 58573298, compound

HRID 2207131Notes

Reaction equation

HRID 2207131 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1.[C:18]([O:23][CH3:24])(=[O:22])[C:19]([CH3:21])=[CH2:20].CC(C)([O-])C.[K+].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(OC(C)C)(=O)C.[Cl-].[Na+]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([C:9]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)=[O:10])[CH2:20][CH:19]([CH3:21])[C:18]([O:23][CH3:24])=[O:22])[CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 6658Methyl MethacrylateHCID 7915Isopropyl AcetateHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 23665647Potassium tert-butoxideHCID 58573710HCID 58573710, compound

Product 1

HCID 58573298HCID 58573298, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

A solution of 2-(3-chlorophenyl)-1-(4-chlorophenyl)ethanone (Step A) (67.4 Kg, 255 mol) in THF (325 L) was dried azeotropically to achieve a water content by Karl Fisher of 0.05 wt %. Methyl methacrylate (25.8 Kg, 257 mol) was added to the solution and the mixture was heated to 45° C. A solution of potassium tert-butoxide (20 wt % in THF, 14.3 Kg, 25 mol) was added over the course of 30 minutes and the mixture was agitated for 6 h. The mixture was cooled to 10° C. and an aqueous solution of citric acid monohydrate (20 wt %, 35 L) was added in less than 5 minutes. Isopropyl acetate (400 L) and an aqueous sodium chloride solution (20 wt %, 300 L) were added. The mixture was agitated for 15 minutes and the phases were separated. The organic phase was distilled under reduced pressure to generate a distillate volume of 560 L while simultaneously adding isopropanol (350 L) and producing a solution of methyl 4-(3-chlorophenyl)-5-(4-chlorophenyl)-2-methyl-5-oxopentanoate in isopropanol (54 wt %, 140 kg total solution mass). The solution had a water content of 0.01 wt % by Karl Fisher. Additional isopropanol (420 L) and sulfuric acid (53 Kg, 535 mol) were added to the solution. The mixture was warmed to reflux and agitated for 12 h, during which time 200 L of solvent were distilled and 200 L of fresh isopropanol were added to the mixture. The mixture was cooled to 20° C. and water (180 L) was added over the course of 30 minutes. Isopropyl acetate (270 L) was added and the mixture was agitated for 30 minutes. The phases were separated and the aqueous phase was extracted using isopropyl acetate (100 L). The combined organic phases were washed with water (200 L) four times. The organic phase was distilled under reduced pressure to generate a distillate volume of 500 L while simultaneously adding isopropanol (50 L) and producing a solution of isopropyl 4-(3-chlorophenyl)-5-(4-chlorophenyl)-2-methyl-5-oxopentanoate in isopropanol (60 wt %, 134 kg total solution mass). The solution had a water content of 0.02 wt % by Karl Fisher. The title material was obtained in 81% overall yield as a roughly 1:1 mixture if diastereoisomers.

Workup

  1. temperatureThe mixture was cooled to 10° C.
  2. stirringThe mixture was agitated for 15 minutes
  3. customthe phases were separated
  4. distillationThe organic phase was distilled under reduced pressure

Sources & evidence

ORD record
ord-b7edc6f8801c4616bc0f55f9a18096fa
Source dataset
uspto-grants-2016_06
Patent number
US09376386B2

Reaction notes

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