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Chemical Structure| 676560-83-1 Chemical Structure| 676560-83-1

Structure of 676560-83-1

Chemical Structure| 676560-83-1

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Product Details of [ 676560-83-1 ]

CAS No. :676560-83-1
Formula : C13H23NO4
M.W : 257.33
SMILES Code : O=C(N1[C@H](C(OCC)=O)CC[C@@H]1C)OC(C)(C)C
MDL No. :MFCD28403536

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Application In Synthesis of [ 676560-83-1 ]

* 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 [ 676560-83-1 ]

[ 676560-83-1 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 676560-83-1 ]
  • [ 334769-80-1 ]
YieldReaction ConditionsOperation in experiment
100% With lithium hydroxide monohydrate; In ethanol; water; for 16h; (2S,5S)-1-(Tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid To a solution of (2S,5S)-1-tert-butyl 2-ethyl 5-methylpyrrolidine-1,2-dicarboxylate (6.46 g, 25.1 mmol) in ethanol (20 mL) was added lithium hydroxide mono hydrate (2.11 g, 50.2 mmol) and deionized water (12 mL). The mixture was allowed to stir for 16 hours then partitioned between ethylacetate and a 1:1 mixture of saturated brine and 1N HCl. The aqueous layer was extracted an additional time with ethyl acetate. The organic layers were combined, dried with sodium sulfate and the solvent was removed in vacuo to yield (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid as a white solid (quant.) and was used directly in the following step.
100% With lithium hydroxide monohydrate; water; In ethanol; for 16h; (2S,5S)-1-(Tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (Compound 1-6) To a solution of (2S,5S)-1-tert-butyl 2-ethyl 5-methylpyrrolidine-1,2-dicarboxylate (6.46 g, 25.1 mmol) in ethanol (20 mL) was added lithium hydroxide monohydrate (2.11 g, 50.2 mmol) and deionized water (12 mL). The mixture was allowed to stir for 16 hours then partitioned between ethylacetate and a 1:1 mixture of saturated brine and 1 N HCl. The aqueous layer was extracted an additional time with ethyl acetate. The organic layers were combined, dried with sodium sulfate and the solvent was removed in vacuo to yield (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid as a white solid (quant.) and was used directly in the following step.
98.5% With lithium hydroxide monohydrate; water; In ethanol; at 25℃; for 12h; [001651 To a solution of compound 1-5 (9.11 g, 35.45 mmol) in EtOH (80 mL) was added a solution of Lithium hydroxide hydrate (2.5 g, 59.67 mmol) in 20 mL of H20 at 25 °C. The mixture was stirred at 25 °C for 12 hours. After the reaction was completed, the mixture was extracted with EtOAc (150 mL), then the EtOAc phase was discarded. The aqueous phase was adjusted to pH 2 with 6percent hydrochloric acid, then the resulting mixture was extracted with EtOAc (80 mLx3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated /n vacuo to give the title compound as a white solid (8.0 g, 98.5percent).The compound was characterized by the following spectroscopic data:MS (ESI, pos.ion) m/z: 230.3 [M+Hfb; and?H NMR (400 MHz, CD3OD): 4.24 (m, 1H), 3.56 (m, 1H), 1.75-1.97 (m, 2H), 1.45-1.69 (m, 2H), 1.40 (s, 9H), 1.32-1.34 (m, 3H) ppm.
98.5% With lithium hydroxide; In ethanol; water; at 25℃; for 12h; Step 5) the Preparation of Compound 1-6 (0231) To a solution of compound 1-5 (9.11 g, 35.45 mmol) in EtOH (80 mL) was added a solution of Lithium hydroxide hydrate (2.5 g, 59.67 mmol) in 20 mL of H2O at 25° C. The mixture was stirred at 25° C. for 12 hours. After the reaction was completed, the mixture was extracted with EtOAc (150 mL), then the EtOAc phase was discarded. The aqueous phase was adjusted to pH 2 with 6percent hydrochloric acid, then the resulting mixture was extracted with EtOAc (80 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as a white solid (8.0 g, 98.5percent). The compound was characterized by the following spectroscopic data: (0232) MS (ESI, pos. ion) m/z: 230.3 [M+H]+; and (0233) 1H NMR (400 MHz, CD3OD): delta 4.24 (m, 1H), 3.56 (m, 1H), 1.75-1.97 (m, 2H), 1.45-1.69 (m, 2H), 1.40 (s, 9H), 1.32-1.34 (m, 3H) ppm.
Example 84A (3.69 g, 14.34 mmol) in 15 mL [OF ETOH] was treated with 14.3 mL of 1.7 N [LIOH] solution at room temperature. After 4 h, the mixture was concentrated, acidified with 1N [HC1] and then extracted with EtOAc (3X). The combined organic extracts were dried with [NA2S04,] and then concentrated to give the crude acid. MS (ESI) [M/Z] 228 (M-H)-.
(d) (2S,5S)-5-Methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester A mixture of the product of the previous step (2 g, 7.77 mmol) and lithium hydroxide (466 mg, 23.3 mmol) in 3:1 methanol:water (24 mL) was stirred at RT overnight, and concentrated. The residue was dissolved in water and extracted with EtOAc (2*20 mL). The aqueous layer was adjusted to pH 2 with 1N HCl and extracted with 3:1 DCM:methanol (3*24 mL) to give the title intermediate (1.7 g) as a white crystal.
With lithium hydroxide monohydrate; water; In ethanol; for 16h; (2S,5S)-l-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid To a solution of (2S,5S)-l -tert-butyl 2-ethyl 5-methylpyrrolidine-l,2-dicarboxylate (6.46 g, 25.1 mmol) in ethanol (20 mL) was added lithium hydroxide mono hydrate (2.11 g, 50.2 mmol) and deionized water (12mL). The mixture was allowed to stir for 16 hours then partitioned between ethylacetate and a 1 : 1 mixture of saturated brine and IN HC1. The aqueous layer was extracted an additional time with ethyl acetate. The organic layers were combined, dried with sodium sulfate and the solvent was removed in vacuo to yield (2S,5S)-l -(tert-butoxycarbonyl)-5-methylpyrrolidine-2- carboxylic acid as a white solid (quant.) and was used directly in the following step.
To a solution of (2S,5S)-1-tert-butyl 2-ethyl 5-methylpyrrolidine-1,2-dicarboxylate (6.46 g, 25.1 mmol) in ethanol (20 mL) was added lithium hydroxide mono hydrate (2.11 g, 50.2 mmol) and deionized water (12 mL). The mixture was allowed to stir for 16 hours then partitioned between ethylacetate and a 1:1 mixture of saturated brine and 1N HCl. The aqueous layer was extracted an additional time with ethyl acetate. The organic layers were combined, dried with sodium sulfate and the solvent was removed in vacuo to yield (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid as a white solid (quant.) and was used directly in the following step.
9.1 g With lithium hydroxide monohydrate; water; In ethanol; for 16h; In the 12g ii-5 prepared in the previous step, add 30ml of ethanol and stir to dissolve.2 g of lithium hydroxide monohydrate and 12 ml of deionized water are added. The mixture was stirred for 16 hours,Add 100ml of saturated sodium chloride solution and acidify with 1N hydrochloric acid;Then add 100ml of ethyl acetate to extract;It is extracted once more with 50 ml of ethyl acetate. The ethyl acetate extracts were combined and dried over anhydrous sodium sulfate overnight. The solid was filtered off and the filtrate was evaporated to dryness under reduced pressure.(9.1 g) of a white solid of (2S,5S)-N-(tert-butoxycarbonyl)-5-methyl-pyrrolidine-2-carboxylic acid (II) was obtained.
9.1 g With lithium hydroxide monohydrate; In ethanol; water; for 16h; Step 5: In 12 g of ii-5 prepared in the previous step, add 30 ml of ethanol, stir to dissolve, add 2 g of lithium hydroxide monohydrate and12ml of deionized water. The mixture was stirred for 16 hours,Add 100ml of saturated sodium chloride solution and acidify with 1N hydrochloric acid; Then add 100ml of ethyl acetate to extract;It is extracted once more with 50 ml of ethyl acetate.The ethyl acetate extracts were combined and dried over anhydrous sodium sulfate overnight.The solid was filtered off and the filtrate was evaporated to dryness under reduced pressure.9.1 g of white solid II was obtained.

 

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