(S)-2-[(tert-Butoxycarbonyl)amino]-3-methylbutanoic acid chloromethyl ester synthesis
- Product Name:(S)-2-[(tert-Butoxycarbonyl)amino]-3-methylbutanoic acid chloromethyl ester
- CAS Number:40224-39-3
- Molecular formula:C11H20ClNO4
- Molecular Weight:265.73
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Yield: 100%
Reaction Conditions:
Stage #1:t-Boc-L-valine with tetra(n-butyl)ammonium hydrogensulfate;sodium hydrogencarbonate in dichloromethane;water at 0; for 0.166667 h;
Stage #2:chlorosulfuric acid chloromethyl ester in dichloromethane;water at 0 - 20; for 19.3333 h;
Steps:
3.I I. Preparation of chloromethyl (tert-butoxycarbonyl)-L-valinate
To a solution of N-Boc-valine (5.00 g, 23.0 mmol, 1.0 eq) in dichloromethane (100 mL) was added sodium bicarbonate (7.74 g, 92.2 mmol, 4.0 eq) and tetrabutylammonium hydrogen sulfate (0.78 g, 2.3 mmol, 0.1 eq) followed by water (100 mL). The mixture was stirred for 10 minutes to allow for dissolution before cooling to 0 °C and adding a solution of chloromethyl chlorosulfate (3.0 mL, 29.0 mmol, 1.3 eq) in dichloromethane (20 mL) dropwise over 20 minutes. The reaction was stirred at 0 °C for 1 hour and then at room temperature for 18 hours. The reaction was partitioned and the aqueous phase was extracted with CH2Cl2 (20 mL). The combined organic phases were washed with water (3 x 100 mL) and brine (100 mL), dried (Na2SO4) and concentrated under reduced pressure to obtain the title compound (6.10 g, quantitative) as a colourless oil; 1H nmr (400 MHz, CDCl3) d 5.87 (1H, d, J 6.0 Hz, 1H of OCH2Cl), 5.61 (1H, d, J 6.0 Hz, 1H of OCH2Cl), 4.97 (1H, br d, J 7.0 Hz, NH), 4.27 (1H, dd, J 9.0, 4.5 Hz, COCHNH), 2.22-2.17 (1H, m, CHCH(CH3)2), 1.44 (9H, s, C(CH3)3), 0.99 (3H, d, J 6.5 Hz, 1x CH3 of CH(CH3)2), 0.92 (3H, d, J 7.0 Hz, 1 x CH3 of CH(CH3)2).
References:
RIGEL PHARMACEUTICALS, INC. WO2021/26451, 2021, A1 Location in patent:Page/Page column 157; 169
49715-04-0
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13734-41-3
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32503-27-8
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40224-39-3
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13734-41-3
543 suppliers
$8.00/1g
40224-39-3
13 suppliers
inquiry