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CAS No. : | 20859-02-3 | MDL No. : | MFCD00064218 |
Formula : | C6H13NO2 | Boiling Point : | - |
Linear Structure Formula : | H2NCH(C4H9)COOH | InChI Key : | NPDBDJFLKKQMCM-SCSAIBSYSA-N |
M.W : | 131.17 | Pubchem ID : | 164608 |
Synonyms : |
(S)-2-amino-3,3-dimethylbutanoic acid
|
Chemical Name : | (S)-2-Amino-3,3-dimethylbutanoic acid |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
70% | (5)-2-(3-fluoro-5-(trifluoromethyl)phenyaniino)-3,3-dimethylbutanoic acid; (5)-2-amino-3,3-dimethylbutanoic acid (0.50 g, 3.81 mmol), K2CO3 (1.580 g, 11.44 mmol), copper(I) iodide (0.073 g, 0.38 mmol) and l-bromo-3-fiuoro-5- (trifluoromethyl)benzene (2.32 g, 9.53 mmol) in DMA (4 mL) was heated at 95 C for 32 hrs. H2O (15 mL) and ethyl ether (20 ml) was added. The aqueous phase was isolated and acidified with saturated KHSO4 solution, extracted with ether, dried over sodium sulfate. After removal of solvent, it gave (S)-2-(3-fluoro-5-(trifluoromethyl)phenylamino)-3,3- dimethylbutanoic acid (0.78 g, 70%) as white solid. LCMS (APCI-): 292.2. 1H NMR (400 MHz, d6-DMSO) delta 12.63 (s, 1H), 6.88 (s, 1H), 6.66 (d, 7=12.4 Hz, 1H), 6.61 (d, J-8.8 Hz, 1H), 6.40 (d, ,/=9.2 Hz, 1H), 3.71 (d, J=9.6 Hz, 1H), 0.98 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6.90 g (77%) | With lithium chloride; caesium carbonate;copper(I) iodide; | General Procedure: (2S)-2-(3-Fluoro-5-trifluoromethyl-phenylamino)-3,3-dimethyl-butanoic acid (450) L-tert-leucine (4.0 g, 30.5 mmol, 1.0 eq.), lithium chloride (129 mg, 3.05 mmol, 0.1 eq.), copper(I) iodide (289 mg, 1.52 mmol, 0.05 eq.) and cesium carbonate (7.5 g, 22.9 mmol, 0.75 eq.) were charged into a 250 mL flask. tert-Butanol (100 mL) was added and the resulting mixture was stirred at 40 C. for 20 minutes, by which time the milky solution had turned blue. 3-Fluoro-5-trifluoromethyl-bromobenzene (7.41 g, 30.5 mmol, 1 eq.) was added dropwise, and the reaction mixture was heated at 100 C. for 15 hours. LCMS analysis of an aliquot showed around 20% (UV) of unreacted 3-Fluoro-5-trifluoromethyl-bromobenzene. Extra copper(I) iodide (289 mg, 0.05 eq.) was added and the reaction mixture was stirred at 100 C. for another 24 hours. LCMS analysis showed ~16% (UV) of remaining 3-Fluoro-5-trifluoromethyl-bromobenzene. Heating was stopped and the solvent removed under vacuum to give a blue solid. The solid was partitioned between ethyl acetate (100 mL) and water (100 mL). The pH of the aqueous phase was adjusted to pH=1 with 4M Hydrochloric acid (10 mL). The organic phase was collected, washed with 2M hydrochloric acid (2*100 mL) dried over sodium sulfate, filtered and the solvent removed under vacuum to give 6.90 g (77%) of the title compound as an orange solid which was used in the next step without further purification. 1H NMR (500 MHz, CHLOROFORM-d) delta ppm 6.61-6.75 (m, 2H) 6.49 (dt, J=10.68, 2.14 Hz, 1H) 4.48 (br. s., 1H) 3.79 (s, 1H) 1.11 (s, 9H) LC-MS: purity 100% (ELS) 90% (UV), tR 2.14 min m/z [M+H]+294.10 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With epichlorohydrin; In toluene; | It was suspended in toluene (50 mL) and epichlorohydrin (5.8 g) was added. The reaction mixture was stirred till the pH was neutral. It was filtered, the solid obtained was stirred with acetone (15 ml*2) and again filtered to obtain L-tert-leucine (5.6 g, 75% yield, 98.5% chemical purity, 99.9% chiral purity). | |
With epichlorohydrin; In toluene; | A mixture of L-tert-leucine.dibenzoyl-d-tartrate salt (27 g) as obtained in Example-1, water (150 mL) and concentrated hydrochloric acid (50 mL) was stirred for 12 hours. The liberated dibenzoyl-d-tartaric acid was filtered and dried (20 g). The filtrate was concentrated under reduced pressure to remove all the solvent. The residue obtained was stirred with acetone (15 ml x 2), filtered and dried to obtain colorless solid <strong>[139163-43-2]L-tert-leucine hydrochloride</strong> salt. It was suspended in toluene (50 mL) and epichlorohydrin (5.8 g) was added. The reaction mixture was stirred until the pH was neutral. It was filtered, the solid obtained was stirred with acetone (15 ml x 2) and again filtered to obtain L-tert-leucine (5.6 g, 75 % yield, 98.5 % chemical purity, 99.9% chiral purity). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine; In toluene; for 12h;Inert atmosphere; Reflux; | [0056] To a mixture of 4-/er/-butylphthalic anhydride (0.514g, 2.52 mmol) and ter/-leucine (0.3g, 2.29 mmol) in anhydrous toluene, triethylamine (0.1 equiv) was added and the mixture was heated to reflux for 12 hours under nitrogen atmosphere. The reaction mixture was then diluted with ethyl acetate, washed with 0. I M HQ solution, dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was then purified on silica gel column chromatography using ethyl acetate-ft-hexane as an eluent to provide a colourless oil (0.7 g, 96%); [a]D25 = -0.35 ( 1 , CHCI3); R/= (1 : 1 ethyl acetate: ??-hexane); 1 H IM MR (400 MHz, CDCI3): delta; 7.88-7.71 (m, 3H, Ar-H), 4.69 (s, 1 H, NCH), 1 .34 (s, 9H, C(CHj)3), 1.15 (s, 9H, C(CHj)3); 1 C NMR (100 MHz, CDCI3): delta 173.3 (COOH ). 168.4, 168.0 (2 x CON), 158.9, 131 .8, 131 .3, 128.9, 123.4, 120.8 (6 x Ar-C), 59.8 (NCH), 35.7, 35.6 (2 x C(CH3)3), 31 .1 , 27.9 (2 x C(CH3)3); IR (film) v 2963, 2873, 171 1 , 1372, 1 101 , 908, 729 cm"1. |