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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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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 156047-39-1 |
Formula : | C8H16FNO2 |
M.W : | 177.22 |
SMILES Code : | CC(C)(F)C[C@H](N)C(OCC)=O |
MDL No. : | MFCD22124918 |
InChI Key : | MJEBOMLXSMSDDI-LURJTMIESA-N |
Pubchem ID : | 11448743 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P264-P270-P271-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P501 |
Class: | 8 |
UN#: | 2735 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
With methanol; potassium carbonate; at 50℃; for 18h; | EXAMPLE 3 4-FLUORO-N-(2,2,2-TRIFLUORO-1-PHENYLETHYL)-L-LEUCINE POTASSIUM SALT 2,2,2-Trifluoroacetophenone (4.24 g, 24.3 mmol) was added to a mixture of <strong>[156047-39-1]L-4-fluoro-leucine ethyl ester</strong> (3.92 g, 22.1 mmol) and K2CO3 (2.90 g, 20.9 mmol) in MeOH (50 mL). The mixture was warmed to 50 C. for 18 h. The mixture was cooled to 20-25 C., filtered and concentrated. The residue was suspended in TBME (100 ml) and filtered to give the title compound as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In acetonitrile; at 0 - 20℃; | To a cold (0C) stirred solution of <strong>[156047-39-1]ethyl 4-fluoro-L-leucinate</strong> (Synlett, 2006, 2, 291, 19.1 g, 107.8 mmol) in acetonitrile (540 mL) was added pyridine (26 mL, 323 mmol) followed by the drop wise addition of benzyl chloroformate (16.9 mL, 118.6 mmol). The reaction was allowed to warm slowly to room temperature and subsequently stirred overnight. EtOAc was added and the mixture was washed with 10% aq. HCl (2x), brine (3x), dried (MgSO4) and concentrated to yield the title compound as an oil.1H NMR (500 MHz, d6-acetone) δ 7.38-7.28 (5H, m), 6.63 (1H, d), 5.17 (2H, s), 4.42-4.35 (1H, m), 4.12 (2H, q), 2.20 (1H, dt), 2.09-2.02 (1H, m), 1.40 (6H, dd), 1.20 (3H, t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In tert-butyl methyl ether; at 20℃; for 3h; | 70% HF-urea (229.7 g, 2.32 mmol) was charged into a HDPE flask at room temperature and then cooled to -10 C to -15 C under nitrogen. (S)-Ethyl 2-amino-4-methylpent-4-enoate, (+)- camphorsulfonic acid salt (150.0 g, 0.39 mmol) was added portion- wise keeping the temperature below 0 C. Slowly warmed the reaction mixture to room temperature and continued the stirring for ~3h at room temperature. After completion of the reaction, the mixture was cooled to -15 C and added to -10 C solution of 30% aqueous ammonia solution keeping the temperature below - 10 C. The precipitated CSA salts were filtered and discarded. The basic aqueous filtrate was extracted with MTBE (3 X 50 mL). The combined MTBE layer was washed with water (50 mL) followed by brine (50 mL). The organic layer was assayed and taken directly for purification with DBDMH. The above obtained crude fluoroleucine in MTBE was charged into a round bottomed flask. Water (10 mL) was added and cooled to 0 - 5 C. l,3-Dibromo-5,5-dimethylhydantoin (DBDMH; 33.13 g; 0.116 mmol) was slowly added keeping the temperature below 0 C. Trifluoroacetic acid (60 mL) was slowly added keeping the temperature below 0 C. Warmed the reaction mixture to RT and stirred for 4 hour. The aqueous layer was separated and extracted the organic layer with IN aqueous HC1 (3 X 25 mL). The combined aqueous layer was carefully pH adjusted to 9.0 to 9.5 with aqueous ammonium hydroxide. The aqueous layer was extracted with MTBE (3 X 50 mL) and the combined organic layer washed with brine and dried over 3A molecular sieves (50 g). The MTBE layer was assayed for (S)-fluoroleucine based on HPLC assay (64.0 g, 60% overall yield from (S)-Ethyl 2-amino-4-methylpent-4- enoate-CSA salt. The MTBE layer containing the Fluoroleucine free base (10.3 g, 58.2 mmol) was charged into a glass lined reactor and cooled to 0 - 5 C. Concentrated sulfuric acid (5.35 g, 54.3 mmol) was slowly added while stirring. After stirring for 3 hours at room temperature the solid was filtered. The wet cake was dissolved in acetonitrile (10 mL) and warmed to 40 C. MTBE (30 mL) was added, the slurry stirred for 3 hours at room temperature and the solid was filtered and dried under vacuum at room temperature to afford the white crystalline sulfate salt in ~ 52% overall yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In ethanol; tert-butyl methyl ether; at 60℃; for 4h; | A suspension of L-tartaric acid (84.7 g, 0.56 mol) and ethanol (300 mL) was heated at 60 C for 30 min and to the resulting clear solution was added (S)-fluoroleucine in MTBE (100 g, 0.56 mol in 300 mL) over 30 minutes. After stirring for 3 h, the suspension was cooled to room temperature and stirred for 30 min. The crystalline solid was filtered, washed with MTBE (100 mL) and dried under vacuum at room temperature for 12 h to afford (S)-fluoroleucine L-tartaric acid salt (166.0 g, 90% yield), 1H NMR (400 MHz, DMSO) δ =7.45 (bs; 5H), 4.13 (q, J = 7.1 Hz, 2H), 4.08 (s, 2H), 3.86(t, J=6.6 Hz, 1H) 2.13-1.96(m, 2H), 1.38(d, J=21.6, 3H), 1.36 (d, J=21.7Hz, 3H), 1.21(t, J=7.1, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | 70% HF-urea (229.7 g, 2.32 mmol) was charged into a HDPE flask at room temperature and then cooled to -10 C to -15 C under nitrogen. (S)-Ethyl 2-amino-4-methylpent-4-enoate, (+)- camphorsulfonic acid salt (150.0 g, 0.39 mmol) was added portion- wise keeping the temperature below 0 C. Slowly warmed the reaction mixture to room temperature and continued the stirring for ~3h at room temperature. After completion of the reaction, the mixture was cooled to -15 C and added to -10 C solution of 30% aqueous ammonia solution keeping the temperature below - 10 C. The precipitated CSA salts were filtered and discarded. The basic aqueous filtrate was extracted with MTBE (3 X 50 mL). The combined MTBE layer was washed with water (50 mL) followed by brine (50 mL). The organic layer was assayed and taken directly for purification with DBDMH. The above obtained crude fluoroleucine in MTBE was charged into a round bottomed flask. Water (10 mL) was added and cooled to 0 - 5 C. l,3-Dibromo-5,5-dimethylhydantoin (DBDMH; 33.13 g; 0.116 mmol) was slowly added keeping the temperature below 0 C. Trifluoroacetic acid (60 mL) was slowly added keeping the temperature below 0 C. Warmed the reaction mixture to RT and stirred for 4 hour. The aqueous layer was separated and extracted the organic layer with IN aqueous HC1 (3 X 25 mL). The combined aqueous layer was carefully pH adjusted to 9.0 to 9.5 with aqueous ammonium hydroxide. The aqueous layer was extracted with MTBE (3 X 50 mL) and the combined organic layer washed with brine and dried over 3A molecular sieves (50 g). The MTBE layer was assayed for (S)-fluoroleucine based on HPLC assay (64.0 g, 60% overall yield from (S)-Ethyl 2-amino-4-methylpent-4- enoate-CSA salt. The MTBE layer containing the Fluoroleucine free base (10.3 g, 58.2 mmol) was charged into a glass lined reactor and cooled to 0 - 5 C. Concentrated sulfuric acid (5.35 g, 54.3 mmol) was slowly added while stirring. After stirring for 3 hours at room temperature the solid was filtered. The wet cake was dissolved in acetonitrile (10 mL) and warmed to 40 C. MTBE (30 mL) was added, the slurry stirred for 3 hours at room temperature and the solid was filtered and dried under vacuum at room temperature to afford the white crystalline sulfate salt in ~ 52% overall yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrakis(tetrabutylammonium)decatungstate(VI); N-fluorobis(benzenesulfon)imide; In water; acetonitrile; for 66h;Inert atmosphere; Sealed tube; UV-irradiation; | [0078] On a larger scale, a solution of (L)-leucine ethyl ester hydrochloride salt (100 mg, 0.51 mmol), TBADT (37 mg, 2%) and NFSI (193 mg, 0.61 mmol) in CH3CN/H20 (2: 1, 6.0 mL) was purged with nitrogen (10 minutes) then sealed. The resulting solution was then placed between two 15 watt UVB (365 nm) lamps and irradiated for 18 hours. At this time, another aliquot of solid NFSI (75 mg) was added to the solution and it was purged with nitrogen for another 10 minutes. The resulting solution was irradiated between two 15 watt UVB (365 nm) lamps for another 24 hours. At this time more solid NFSI (50 mg) was added to the solution and it was purged with nitrogen for another 10 min, and irradiated for a further 24 hours, and then worked up as follows: The blue solution was diluted with CHC13 and water/potassium carbonate was added to pH >10. The solvent was removed via rotary evaporator and the resulting white solid was suspended in CHCI3 and dried over MgSC>4. The solution was cooled in a freezer and then filtered over celite, washing with cold CHCI3. Concentration of the filtrate yielded an orange oil (68 mg) that was -75% pure based on H NMR analysis. The approximate isolated yield of ( |