Structure of H-DL-Val-OtBu
CAS No.: 6070-59-3
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CAS No. : | 6070-59-3 |
Formula : | C9H19NO2 |
M.W : | 173.25 |
SMILES Code : | CC(C)[CH](N)C(OC(C)(C)C)=O |
MDL No. : | MFCD03548062 |
InChI Key : | RJBVJBGFJIHJSZ-UHFFFAOYSA-N |
Pubchem ID : | 4532027 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362 |
* 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 perchloric acid; at 20℃; for 36h; | Step 1: tert-butyl 2-amino-3-methylbutanoateTo a stirred solution of DL- valine (25 g, 0.213 mol) in tert-butyl acetate (250 mL) at 0C, was added HCI04 (64.2 g, 0.320 mol) portionwise. The reaction mixture was stirred for 36 h at RT. It was diluted with water and extracted in ethyl acetate (500 mL). The organic layer was washed with a 10% sodium bicarbonate solution (2x150 mL), dried over Na2S04 and concentrated, affording of the title compound as brown liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.31 (brs, 2H), 3.62(d, J = 4.4 Hz, 1 H), 1 .98 (d, J = 1.7 Hz, 1 H), 1.44(s, 9H), 0.95 (m, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95-97% | Example 9 The same operation as in Example 6 was carried out, but starting with t-butyl (RS)-valinate. (R)-Valine was obtained with a 95-97% yield and an ee=98-99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere; | Step 2 : tert-butyl 2-[(4-cyano-2-fluorobenzyl) amino]-3-methylbutanoateTo a stirred solution of <strong>[6070-59-3]tert-butyl 2-amino-3-methylbutanoate</strong> (8.5 g, 0.05 mol)in dry DMF (50 mL) under nitrogen, was added 4-cyano-2-fluoro-benzyl bromide (FluoroChem Ltd, 9.4 g, 0.044 mol) and NaHC03 (10.2 g, 0.12 mol). The resulting mixture was stirred at RT for 16 h. Water (70 mL) was added and the desired product was extracted with ethyl acetate (2x100 mL). The organic layer was washed with water (3x100 mL) and the solvent was dried over Na2S04 and concentrated under vacuum. The resulted residue was purified by column chromatography using petroleum ether/ ethyl acetate as eluent, affording of the title compound as colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.77 (d, J = 10.2 Hz, 1 H), 7.67 (t, J = 1 .5 Hz, 1 H), 3.85-3.79 (m, 2H), 2.72 (m, 1 H), 2.49 (m, 1 H), 1.81 (m, 1 H), 1.37(s, 9H), 0.86 (m, 6H). | |
With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere; | Step 1: 1- tert-butyl 2-[(4-cyano-2-fluorobenzyl)amino]-3-methylbutanoateTo a stirred solution of <strong>[6070-59-3]tert-butyl 2-amino-3-methylbutanoate</strong> (Bachem, 6.3 g, 0.036 mol) in dry DMF (50 mL) under nitrogen, was added 4-cyano-2-fluoro- benzyl bromide (6.2 g, 0.029 mol) and NaHC03 (6.09g, 0.073 mol). The resulting mixture was stirred for 16 h at RT. Water (70 mL) was added and extracted with ethyl acetate (2x100 mL). The organic layer was washed with water (3x100mL) and the solvent was dried over Na2S04 and concentrated under vacuum. The resulted residue was purified by column chromatography using petroleum ether/ ethyl acetate as eluent, affording the title compound as colorless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.78 (d, J = 10.2 Hz, 1 H), 7.67 (t, J = 1.5 Hz, 2H) 3.81 (m, 2H), 2.71 (m, 1 H), 2.49 (m 1 H), 1 .81 (m, 1 H), 1 .37 (s, 9H), 0.88-0.84 (m, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 70℃; for 16h;Inert atmosphere; | Step 1: tert-butyl 2-[(4-cyano-2-fluorobenzyl)amino]-2-methylpropanoateTo a stirred solution of tert-butyl 2-amino-2-methylpropanoate (Bachem, 7.9 g, 0.05 mol) in dry DMF (50 mL) under nitrogen, was added 4-cyano-2-fluoro benzyl bromide (10.6 g, 0.05 mol) and NaHC03 (8.3 g, 0.099 mol) as a solid. The reaction mixture was stirred for 16 h at 70C. Water (70 mL) was added and extracted with ethyl acetate (100 mL). The organic layer was washed with water (3x100 mL) and the solvent was dried over Na2S04 and concentrated under vacuum. The residue was purified by column chromatography using silica gel (60-120 mesh) and petroleum ether/ ethyl acetate as eluent, affording the title compound as colourless liquid. 1H NMR (DMSO-de, 400 MHz) δ 7.78 (d, J = 10.0 Hz, 1 H), 7.71 -7.65 (m, 2H), 3.69 (d, J = 6.9 Hz, 2H), 2.55 (s, 1 H), 1 .44 (s, 9H), 1 .19 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃;Product distribution / selectivity; | To the solution of valine tert-butyl ester 419.4 mg (2 mmol) in DCM 14 ml, triphosgene 1.78 g (6 mmol) andtriethylamine 2.8 ml (20 mmol) were added and stirred at room temperature overnight. The reaction mixture was washed with saturated sodium bicarbonate 30 ml, water 30 ml, and brine 30 ml. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated in vacuo to obtain tert-butyl 2-isocyanato-3-methylbutanoate .To the solution of ( 6S, 9S) -N-benzyl-6- (4-hydroxybenzyl) -2, 9-dimethyl-4 , 7-dioxo-8- (quinolin-8-ylmethyl ) octahydro-lH- pyrazi o [2, 1-c] [1, 2, 4] triazine-l-carboxamide 964.4 mg (1 mmol) in DCM 12 ml, triethylamine 0.07 ml (0.5 mmol) and .tert-butyl 2-isocyanato-3-methylbutanoate were added and stirred at room temperature overnight. The reaction mixture was washed with saturated sodium bicarbonate 30 ml, water 30 ml, and brine 30 ml. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by Buchi silica gel column chromatography (chloroform:methanol=100 : 0 to 98:2) to obtain tert-butyl 2- ( (4- ( ( (6S., 9S) -1- (benzylcarbamoyl) -2, 9-dimethyl-4 , 7-dioxo-8- (quinolin-8-ylmethyl) octahydro-lH-pyrazino [2,1- c] [1,2,4] triazin-6-yl ) methyl ) phenoxy) carbonylamino) -3- methylbutanoate 787 mg (61%).To the tert-butyl 2- ( (4- (( (6S, 9S) -1- (benzylcarbamoyl) -2, 9-dimethyl-4 , 7-dioxo-8- (quinolin-8-ylmethyl) octahydro-lH- pyrazino [2 , 1-c] [1, 2, 4] triazin-6- yl ) methyl) phenoxy) carbonylamino) -3-methylbutanoate 787 mg (1 mmol) , trifluoroacetic acid 6 ml and DCM 6 ml were added and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate 30 ml and washed with water 30 ml, and brine 30 ml. The organic layer was dried withmagnesium sulfate and filtered. The filtrate was concentrated in vacuo to obtain title compound 705mg (96 %) . |