2-Deoxy-alpha-D-erythropentofuranosyl chloride 3,5-bis(4-methylbenzoate) synthesis
- Product Name:2-Deoxy-alpha-D-erythropentofuranosyl chloride 3,5-bis(4-methylbenzoate)
- CAS Number:4330-21-6
- Molecular formula:C21H21ClO5
- Molecular Weight:388.84
4330-34-1
4330-21-6
Under argon protection, (2R,3S)-5-methoxy-2-(((4-methylbenzoyl)oxy)methyl)tetrahydrofuran-3-yl 4-methylbenzoate (50.0 g, 0.13 mol) was dissolved in glacial acetic acid (150 mL) and stirred at room temperature for 20 min. The reaction solution was cooled to 10-15 °C and a dioxane solution (150 mL, 0.6 mol) in 4 M HCl was slowly added dropwise for a controlled time of 5 min. After observing a light straw color to the solution, a small amount of 1-Α-chloro-3,5-di-O-tosyl-2-deoxy-D-ribofuranose crystal species was added and stirred briefly until a precipitate appeared. Stirring was stopped and the reaction mixture was allowed to stand for 40 minutes while being kept cool with an ice water bath. The white slurry was broken up by swirling the flask and quickly filtered. The resulting filter cake was washed with cold ether (3 x 30 mL) and dried under high vacuum to afford the target product 1-Α-chloro-3,5-di-O-p-toluoyl-2-deoxy-D-ribofuranose (34.1 g, 67% yield) as a white solid. The spectral data and analytical results of the product were in agreement with those reported in the literature. Thin layer chromatography (TLC) Rf value was 0.58 (Expanding agent: ethyl acetate-hexane, 1:2). Infrared spectra (IR, cm-1): 3030, 2951, 1708, 1276, 1178, 1099, 755. nuclear magnetic resonance hydrogen spectrum (1H NMR, 250.1 MHz, CDCl3): δ 2.41 (s, 3H, CH3), 2.42 (s, 3H, CH3), 2.74 (m, 1H, 2-CH), 2.84 (m 1H, 2-CH), 4.61 (dd, J=12.1,4.1 Hz, 1H, 5-CH), 4.66 (dd, J=12.1,4.1 Hz, 1H, 5-CH), 4.85 (m, 1H, 4-CH), 5.58 (m, 1H, 3-CH), 6.47 (d, J=4.2 Hz, 1H, 1-CH), 7.24 (d, J=8.3 Hz, 2H, 3,5-tol-CH), 7.26 (d, J=8.3 Hz, 2H, 3,5-tol-CH), 7.90 (d, J=8.3 Hz, 2H, 2,6-tol-CH), 7.99 (d, J=8.3 Hz, 2H, 2,6-tol-CH). Nuclear magnetic resonance carbon spectrum (13C NMR, 62.9 MHz, CDCl3): δ 21.70 (CH3), 21.71 (CH3), 44.54 (2-CH2), 63.51 (5-CH2), 73.56 (4-CH), 84.71 (3-CH), 95.3 (1-CH), 126.66 (C), 126.72 ( C), 129.19 (CH), 129.21 (CH), 129.63 (CH), 129.88 (CH), 144.07 (C), 144.30 (C), 166.07 (CO), 166.41 (CO). Mass spectra (EI): m/z (relative abundance) 353 ([M-Cl]+, 1), 252 (1), 216 (32), 136 (38), 119 (100), 91 (78), 81 (100), 65 (28), 53 (25), 39 (19). Calculated elemental analysis (C21H22ClO5): C, 64.8; H, 5.41. Measured values: C, 64.4; H, 5.39.
78185-64-5
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4330-21-6
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Yield:4330-21-6 58%
Reaction Conditions:
with hydrogenchloride;glacial acetic acid;acetyl chloride at 20; for 0.5 h;
Steps:
2.3 Synthesis of compound 4
To a solution of (2R,3S,5S)-5-methoxy-2-(((4- methylbenzoyl)oxy)methyl)tetrahydrofuran-3-yl 4-methylbenzoate (250 g, 0.65 mol, 1 eq) in acetic acid (393 mL) was added a freshly prepared solution of saturated HC1 in acetic acid (using acetyl chloride and acetic acid) (618 mL) slowly at room temperature. After completion of the addition, further acetyl chloride (50 mL) was added slowly at room temperature. The reaction mixture was stirred for a further 30 minutes, upon which time a colourless precipitate formed that was isolated by filtration to give (2R,3S,5R)-5-chloro-2- (((4-methylbenzoyl)oxy)methyl)tetrahydrofuran-3-yl 4-methylbenzoate as a colourless solid (145 g, 58 %). LCMS: 407 ( 8.10 - 7.84 (m, 5H), 7.34 - 7.20 (m, 5H), 6.52 (d, J = 5.1 Hz, 1H), 5.61 (ddd, J = 7.4, 2.8, 1.1 Hz, 1H), 4.91 (q, J = 3.5 Hz, 1H), 4.75 - 4.61 (m, 2H), 2.92 (ddd, J = 15.0, 7.5, 5.2 Hz, 1H), 2.79 (dd, J = 15.2, 1.1 Hz, 1H), 2.47 (d, J - 4.8 Hz, 6H).
References:
WO2022/81739,2022,A1 Location in patent:Page/Page column 32-33
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4330-21-6
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