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Product Details of (R)-(-)-Glycidyl butyrate

CAS No. :60456-26-0
Formula : C7H12O3
M.W : 144.17
SMILES Code : [C@H]1(OC1)COC(=O)CCC
MDL No. :MFCD00075120
InChI Key :YLNSNVGRSIOCEU-ZCFIWIBFSA-N
Pubchem ID :2724536

Safety of (R)-(-)-Glycidyl butyrate

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H341-H227
Precautionary Statements:P501-P261-P270-P202-P210-P201-P271-P264-P280-P370+P378-P308+P313-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330-P302+P352+P312-P304+P340+P312-P403+P235-P405

Application In Synthesis of (R)-(-)-Glycidyl butyrate

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 60456-26-0 ]
  • Downstream synthetic route of [ 60456-26-0 ]

[ 60456-26-0 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 1220910-89-3 ]
  • [ 60456-26-0 ]
  • [ 856866-72-3 ]
YieldReaction ConditionsOperation in experiment
86.7%
Stage #1: With potassium <i>tert</i>-butylate; lithium tert-butoxide In tetrahydrofuran; acetonitrile at 25℃; for 2 h; Inert atmosphere
Stage #2: for 3 h;
In a 1L three-necked bottle, 50 g of a compound of Formula X3, 400 ml of tetrahydrofuran and 400 ml of acetonitrile were added.Nitrogen gas, temperature 25°C, solids insolubleThen, 9.9 g of lithium tert-butoxide and 13.9 g of potassium tert-butoxide were added, and the solid matter dissolved.The reaction solution changed from colorless to yellow,After stirring for 2 hours, the reaction solution was added dropwiseR-(-)-glycidol butyric acid and compound of formula R 19.7 g,After completion of the addition, the reaction was incubated for 3 hours, and the sample was subjected to a TLC (developing solvent: chloroform/methanol = 10/1). After the spot of the compound of Formula X3 disappeared, the sample was dropped.Add dilute hydrochloric acid prepared from concentrated hydrochloric acid and water, adjust the pH to 8, fully stir for 30 minutes, the water bath temperature is 35°C to 55°C, and the vacuum degree -0.07MPa to -0.1MPa is concentrated under reduced pressure to stop flow.
85%
Stage #1: With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 1.41667 h; Inert atmosphere
Stage #2: With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone In tetrahydrofuran at 20℃; for 15 h; Inert atmosphere; cooling with ice
A 5-L, three-neck, round-bottom flask was equipped with an overhead stirrer, a thermocouple, a 500-mL addition funnel and a nitrogen-inlet adapter. The flask was dried with a heat gun under a flow of nitrogen to an internal temperature of 60°C. The flask was charged with intermediate 7 (110.0 g, 0.272 mol, AMRI lot No. DUG-AF-202Q)) and anhydrous THF (2.2 L, 20 vol). The slurry was stirred and a light green solution formed. The addition funnel was charged with 1.0 M lithium hexamethyldisilazide (299 mL, 0.286 mol, 1.05 eq.). The LiHMDS solution was added dropwise to the solution of intermediate 7 over approximately 25 minutes. A red solution formed. The solution was stirred one hour at room temperature and then DMPU (34.9 g, 0.272 mol, 1 eq) was added, and the mixture turned to a yellow slurry. The batch was cooled in an ice bath to 5.7°C. R-(-)-Glycidyl butyrate (41.25 g, 0.286 mol, 1.05 eq) was then added in one portion. The mixture was stirred in the ice bath for 0.5 hour and then was warmed to room temperature and stirred overnight. The reaction formed a tan slurry at this point, and HPLC analysis after 15 hours indicated that there was approximately 87percent TR-700, 1.6percent intermediate 7, and approximately 7percent of the butyrate ester of TR-700. A small amount of sodium methoxide in methanol (11 mL, 0.1 vol) was added, and the batch was stirred for 1 hour to remove the residual ester. The in-process HPLC analysis at this point showed there was approximately 90.7percent TR-700 and 0.2percent of the butyrate ester. The reaction was quenched by the addition of 10percent w/w ammonium chloride solution (1.1 L, 10 vol). A modest exothermic event from 22°C to 25°C was observed upon addition of the ammonium chloride solution. The two-phase mixture was distilled to a pot temperature of 700C (atmospheric pressure) to remove approximately 2.2 L of the THF. This formed a thick slurry which is diluted with water (550 mL, 5 volumes). The slurry was cooled to room temperature (23.6°C) and was filtered. The filter cake was washed with water (1.1 L, 10 vol) and methanol (550 mL, 5 vol) to give TR-700 as a white solid. The wet cake was dried overnight in a vacuum oven at 500C to give 89.7 g of TR-700 (89percent yield) that was 97.8percent (AUC) by HPLC analysis. The TR-700 was further purified by reslurrying in 2.7 L (30 vol) of 4: 1 methanol/water at 700C, cooling to 230C, filtering and washing with methanol (180 ml). This removed some of the over-alkylated product that is observed. The purified TR- 700 was recovered in 96percent yield (85percent overall yield), and the purity was improved to 98.4percent (AUC) by HPLC analysis. The palladium content was 10 ppm.
References: [1] Patent: CN107722056, 2018, A, . Location in patent: Paragraph 0058; 0060; 0062; 0063; 0064; 0068.
[2] Patent: WO2010/42887, 2010, A2, . Location in patent: Page/Page column 19-20.
 

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