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Chemical Structure| 20143-48-0

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Product Details of [ 20143-48-0 ]

CAS No. :20143-48-0
Formula : C10H11ClO2
M.W : 198.65
SMILES Code : O=C(Cl)COC1=C(C)C=CC=C1C

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Application In Synthesis of [ 20143-48-0 ]

* 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.

  • Downstream synthetic route of [ 20143-48-0 ]

[ 20143-48-0 ] Synthesis Path-Downstream   1~4

  • 1
  • (2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane (S)-pyroglutamic acid salt [ No CAS ]
  • [ 20143-48-0 ]
  • [ 192725-17-0 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In water; ethyl acetate; at 20 - 25℃; for 1.41667h;Product distribution / selectivity; The product obtained in Stage-3 (50 g, 0.084 mol) was added to a mixture of ethyl acetate (375 ml) and DM water (375 ml). Sodium bicarbonate (41.22 g, 0.49 mol) was added and stirred for 15 min at 20-25 C. Thereafter, the solution of acid chloride prepared in step-1 of Stage-4 was added in 10 min while maintaining a vigorous stirring at 20-25 C. After stirring for 1 h at 20-25 C., the organic layer was separated and washed with 5% aq sodium bicarbonate (250 ml) followed by 10% aq sodium chloride solution (250 ml). The organic layer was treated with activated carbon (5 g) for 15 min. The carbon was filtered off through hyflo and washed with ethyl acetate (50 ml). The combined filtrate was concentrated at 50-55 C. under reduced pressure to dryness and the resulting residue was dissolved in ethyl acetate (250 ml) and taken to dryness. The residue obtained was dissolved in ethyl acetate (250 ml) at 50-60 C. and added heptanes (250 ml). The reaction mass was stirred at 50-55 C. for an additional 1 h and the resulting slurry was cooled to room temperature. After stirring the crystallized product for 5 h at room temperature the product was isolated by filtration and washed with a mixture of ethyl acetate (50 ml) and heptanes (50 ml). The wet product was dried under reduced pressure at 50 C. to obtain 45 g of Lopinavir.
90 g With sodium hydrogencarbonate; In water; ethyl acetate; at 25 - 35℃; for 1h; 2,6-dimethylphenoxyacetic acid (28.7 g), ethyl acetate (100 mL), thionyl chloride (25 g) and dimethyl formamide (1 mL) were charged in reaction flask at 25-35C. Reaction mass was heated to 50-55C and stirred for 2-3 hrs at same temperature, and then added to a mixture of pyroglutamic acid salt of Formula VI (100 g), ethyl acetate (750 mL), water (750 mL) and sodium bicarbonate (82.5 g) at 25-35C and stir for 60 min at same temperature. After completion of the reaction, organic layer was separated and treated with 5% sodium bicarbonate solution (25 g dissolved in 500 mL). Then the organic layer was separated and concentrated under vacuum at below 60C to get the title compound as a residue. Yield: 100 g; HPLC purity: 99%; Formula D by HPLC: 0.15%; Formula E by HPLC: Not detected; and Formula F by HPLC: 0.8%. (0179) The above lopinavir (100 g) was dissolved in methanol (300 mL) and ammonia (100 mL) was charged and the reaction mass was heated to 40-45C for 1-2 hrs at same temperature. After completion of the reaction, solvent was concentrated under vacuum at below 60C to obtain residue. To the obtained residue methylene chloride (400 mL) and water (200 mL) were charged at 25-35C. Then the product containing organic layer was speared and concentrated under vacuum at below 45C. The obtained solid was dissolved in acetone (200 mL) at 50-55C for 30-60 min. Reaction mass was gradually cool to 0- 5C and the precipitated solid was filtered and washed with chilled acetone (100 mL) and dried at 30-35C under vacuum to get the title compound. Yield: 90 g; HPLC purity: 99.9%; Formula A by HPLC: Not detected; Formula B by HPLC: Not detected; Formula C by HPLC: Not detected; Formula D by HPLC: 0.02%; Formula E by HPLC: Not detected; and Formula F by HPLC: Not detected.
  • 2
  • [ 192726-05-9 ]
  • [ 20143-48-0 ]
  • [ 192725-17-0 ]
  • 3
  • [ 20143-48-0 ]
  • [ 192725-45-4 ]
YieldReaction ConditionsOperation in experiment
Succinate salt obtained from example 3 was added portion wise to a vigorously stirred mixture of sodium bicarbonate (4.7 g) in water (40 mL) and ethyl acetate (30 mL) at room temperature over a period of 10 minutes. On stirring at room temperature for 30 minutes, the reaction mixture became almost homogeneous, however suddenly a white solid separated out from the upper ethyl acetate layer. To a cooled at about 15 0C, of the above suspended reaction mixture, a solution of acid chloride in ethyl acetate (from step 1 of example 4) at 15-200C was slowly added over about 15 minutes. The resulting mixture was stirred at room temperature for 1.5 hours. After 1 hour stirring at room temperature, a white solid again precipitated out from the solution. Ethyl acetate (30 mL) was added and stirred for next 30 minutes. After separating the organic layer, the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layer was washed successively with aqueous sodium hydroxide (2 X 20 mL), hydrochloric acid (2 X 20 mL), water (1 X 20 mL) and brine (1 X 20 mL). It was then filtered through hyfio bed and dried over sodium sulfate. Concentration of ethyl acetate solution under reduced pressure resulted the title compound as an off-white solid.Yield: 5.6 g
  • 4
  • (2S,3S,5S)-2-amino-3-hydroxy-5-(2S-(1-tetrahydropyramid-2-only)-2-methylbutanoyl)-amino-1,6-diphenylhexane [ No CAS ]
  • [ 20143-48-0 ]
  • [ 192725-17-0 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In water; ethyl acetate; at 20 - 25℃; for 1.16667h; The product obtained in Stage-3 (50 g, 0.084 mol) was added to a mixture of ethyl acetate (375 ml) and DM water (375 ml). Sodium bicarbonate (41 .22 g, 0.49 mol) was added and stirred for 15 min at 20-250C. Thereafter, the solution of acid chloride prepared in step- 1 of Stage-4 was added in 10 min while maintaining a vigorous stirring at 20-250C. After stirring for I h at 20-250C, the organic layer was separated and washed with 5% aq sodium bicarbonate (250 ml) followed by 10% aq sodium chloride solution (250 ml). The organic layer was treated with activated carbon (5 g) for 15 min. The carbon was filtered off through hyflo and washed with ethyl acetate (50 ml). The combined filtrate was concentrated at 5O-55C under reduced pressure to dryness and the resulting residue was dissolved in ethyl acetate (250 ml) and taken to dryness. The residue obtained was dissolved in ethyl acetate (250 ml) at 50-600C and added heptanes (250 ml). The reaction mass was stirred at 5O-55C for an additional 1 h and the resulting slurry was cooled to room temperature. After stirring the crystallized product for 5 h at room temperature the product was isolated by filtration and washed with a mixture of ethyl acetate (50 ml) and heptanes (50 ml). The wet product was dried under reduced pressure at 5O0C to obtain 45 g of Lopinavir. Purity of Lopinavir: 99.5% by HPLC
 

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