Structure of 955379-18-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| CAS No. : | 955379-18-7 |
| Formula : | C11H21NO5 |
| M.W : | 247.29 |
| SMILES Code : | O=C(OC(C)(C)C)NC(C(=O)OC(C)C)CO |
| English Name : | Isopropyl (tert-butoxycarbonyl)serinate |
| MDL No. : | N/A |
* 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.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | With pyridine In dichloromethane at 20℃; for 2h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 96% | With methanesulfonyl chloride; triethylamine In dichloromethane at 0 - 20℃; for 4h; | 1 Step 1 Synthesis of isopropyl 2-((tert-butoxycarbonyl)amino)acrylate H5-1a To a stirred solution of isopropyl (tert-butoxycarbonyl)serinate (50 g, 202.4 mmol) and TEA (84 ml_, 607 mmol) in DCM (500 ml_) at 0 °C was added methane sulfonyl chloride (23.38 ml_, 303.3 mmol) dropwise and the resultant the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was quenched with ice water (200 ml_) and extracted with DCM (300 ml_). Organic layer was separated, dried over anhydrous Na2S04 and concentrated under reduced pressure to obtained crude material, which was purified by Biotage-lsolera using silica snap (230-400 mesh) and eluted with (0-10 %) EtOAc in petroleum-ether gradient to afford isopropyl 2-((tert-butoxycarbonyl)amino)acrylate H5-1a as a colourless gum (45g, 96%). 1H NMR (400MHz, DMSO-d6) d: 8.36 (s, 1 H), 5.60 (s, 1 H), 5.46 (s, 1 H), 5.0 - 4.94 (m, 1 H), 1.42 (s, 9H), 1.24 (d, J= 6.4 Hz, 6H) |
| 93% | With methanesulfonyl chloride; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; | 1 Isopropyl 2-((tert-butoxycarbonyl)amino)acrylate (7) To a solution of 1 (10.05 g, 40.6 mmol) in DMF (100 mL) was added MsCl (4.12 mL, 52.8 mmol) under ice-cooling. Triethylamine (14.16 mL, 102.0 mmol) was then added dropwise via an addition funnel over 30 min, while maintaining the reaction temperature between 0-5° C. When the addition was complete, the cooling bath was removed and the yellow heterogeneous reaction mixture was aged at room temperature under N2 for overnight. The reaction mixture was diluted with ice cold water (1 L) and MTBE (1 L). The layers were separated and the aqueous layer was back-extracted with MTBE (500 mL). The organic layers were combined and washed with 1M citric acid (750 mL), water (1 L) and then 10% aqueous NaCl (1 L). The organic solution contained 7 (8.652 g, 93% yield). Solvent was switched to DMSO at <40° C. and use solution directly in next step. |
| 80% | With dmap; 1,8-diazabicyclo[5.4.0]undec-7-ene; p-toluenesulfonyl chloride In acetonitrile at 20℃; Molecular sieve; | General procedure for preparation of dehydroamino acid (or dehydrodipeptide) General procedure: 4-Toluenesulfonic chloride (TsCl) (2.0 eq) and 4-dimethylaminopyridine (DMAP) (0.2 eq) were added subsequently to the solution of N-Boc-DL-Ser-O-Me (1.0 eq) in acetonitrile (0.2 M, containing MS (4Å) (40 mg/mmol)) at r.t., 1,8-diazobicyclo[5,4,0]undec-7-ene (DBU) (5.0 eq) was added dropwisely to the solution, whose color darkened during the addition, the reaction was monitored by thin layer chromatography (TLC). When starting material was consumed, the mixture was diluted with ethyl acetate, washed with saturated citric acid, followed by water, then by brine. The organic phase was dried over anhydrous sodium sulfate. Crude product was obtained after concentration, which was purified through flash chromatography. |
| Multi-step reaction with 2 steps 1: 79 percent / pyridine / CH2Cl2 / 2 h / 20 °C 2: 81 percent / K2CO3 / dimethylformamide / 1 h / 65 °C | ||
| 4.5 g | With methanesulfonyl chloride; triethylamine In dichloromethane at 0 - 20℃; for 1.33333h; | |
| Multi-step reaction with 2 steps 1: triethylamine / dichloromethane; water / 1 h / 20 °C 2: triethylamine / tetrahydrofuran / 30 h / 15 - 20 °C | ||
| Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 1 h / 20 °C 2: methanesulfonyl chloride; triethylamine / N,N-dimethyl-formamide / 0 - 20 °C | ||
| With methanesulfonyl chloride; triethylamine In N,N-dimethyl-formamide | ||
| Multi-step reaction with 2 steps 1: triethylamine / N,N-dimethyl-formamide / 0 °C 2: methanesulfonyl chloride; triethylamine |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91.7% | With triethylamine In dichloromethane at 20℃; Cooling with ice; | 1.2 N-tert-butoxycarbonylserine isopropyl ester Taking the above-mentioned example 1 step 1 obtained in the 6.00g serine isopropyl ester hydrochloride in DCM, then dropwise 8.25g Et3N. Under ice bath then adding 8.64g Boc2O, then the reaction at room temperature overnight. Water, liquid, organic layer salt water washing, drying, column shall be 7.41g white solid (N - tert-butoxycarbonyl - serine isopropyl ester), yield 91.7%. |
| With triethylamine In tetrahydrofuran at 20℃; for 5h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: triethylamine / dichloromethane; water / 1 h / 20 °C 2: sodium iodide / acetone / 17 - 29 °C | ||
| Multi-step reaction with 2 steps 1: triethylamine / N,N-dimethyl-formamide / 0 °C 2: sodium iodide / acetone |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 3 steps 1: triethylamine / dichloromethane; water / 1 h / 20 °C 2: sodium iodide / acetone / 17 - 29 °C 3: caesium carbonate / N,N-dimethyl-formamide / 10.5 h / 5 - 15 °C | ||
| Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 1 h / 20 °C 2.1: methanesulfonyl chloride; triethylamine / N,N-dimethyl-formamide / 0 - 20 °C 3.1: caesium carbonate / dimethyl sulfoxide / 0.67 h / 18 - 22 °C / Inert atmosphere 3.2: 2 h / 18 - 22 °C | ||
| Multi-step reaction with 2 steps 1: methanesulfonyl chloride; triethylamine / N,N-dimethyl-formamide 2: caesium carbonate / dimethyl sulfoxide |
| Multi-step reaction with 3 steps 1: triethylamine / N,N-dimethyl-formamide / 0 °C 2: sodium iodide / acetone 3: caesium carbonate / N,N-dimethyl-formamide / 15 °C | ||
| Multi-step reaction with 3 steps 1: triethylamine / N,N-dimethyl-formamide / 0 °C 2: methanesulfonyl chloride; triethylamine 3: caesium carbonate / dimethyl sulfoxide |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 4 steps 1: triethylamine / dichloromethane; water / 1 h / 20 °C 2: sodium iodide / acetone / 17 - 29 °C 3: caesium carbonate / N,N-dimethyl-formamide / 10.5 h / 5 - 15 °C 4: potassium carbonate; potassium formate; 10% Pd/C / isopropyl alcohol / 2 h / 60 °C | ||
| Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 1 h / 20 °C 2.1: methanesulfonyl chloride; triethylamine / N,N-dimethyl-formamide / 0 - 20 °C 3.1: caesium carbonate / dimethyl sulfoxide / 0.67 h / 18 - 22 °C / Inert atmosphere 3.2: 2 h / 18 - 22 °C | ||
| Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / 1 h / 20 °C 2.1: methanesulfonyl chloride; triethylamine / N,N-dimethyl-formamide / 0 - 20 °C 3.1: caesium carbonate / dimethyl sulfoxide / 0.67 h / 18 - 22 °C / Inert atmosphere 3.2: 2 h / 18 - 22 °C 4.1: potassium carbonate; potassium formate; 10% Pd/C; isopropylamine / 2 h / 60 °C |
| Multi-step reaction with 2 steps 1: methanesulfonyl chloride; triethylamine / N,N-dimethyl-formamide 2: caesium carbonate / dimethyl sulfoxide / 20 °C | ||
| Multi-step reaction with 3 steps 1: methanesulfonyl chloride; triethylamine / N,N-dimethyl-formamide 2: caesium carbonate / dimethyl sulfoxide 3: potassium carbonate; potassium formate; Pd/C / Isopropyl acetate / 60 °C | ||
| Multi-step reaction with 3 steps 1: triethylamine / N,N-dimethyl-formamide / 0 °C 2: methanesulfonyl chloride; triethylamine 3: caesium carbonate / dimethyl sulfoxide / 20 °C | ||
| Multi-step reaction with 4 steps 1: triethylamine / N,N-dimethyl-formamide / 0 °C 2: sodium iodide / acetone 3: caesium carbonate / N,N-dimethyl-formamide / 15 °C 4: potassium carbonate; potassium formate; Pd/C / Isopropyl acetate / 60 °C | ||
| Multi-step reaction with 4 steps 1: triethylamine / N,N-dimethyl-formamide / 0 °C 2: methanesulfonyl chloride; triethylamine 3: caesium carbonate / dimethyl sulfoxide 4: potassium carbonate; potassium formate; Pd/C / Isopropyl acetate / 60 °C |
