반응 #164435

반응 방정식

N-Acetyl-β-neuraminic Acid Benzyl ester

Carbobenzyloxy-L-Valine

1-Chloro-N,N,-2-trimethyl-1-propenylamine

→

( 1-5 )

수율 32.0%

5-Acetylamino-6-[3-(2-benzyloxycarbonylamino-3-methyl-butyryloxy)-1,2-dihydroxy-propyl]-2,4-dihydroxy-tetrahydro-pyran-2-carboxylic acid benzyl ester

수율 32.0%

용매

pyridine

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONby dropwise addition via a syringe
2. 2
   기타resulting in a clear colorless solution
3. 3
   workup.WAITThe solution immediately turns yellow and is kept at 0° C. and under an argon atmosphere for 3 hours
4. 4
   기타The cooling bath is then removed
5. 5
   workup.WAITthe solution kept at rt for overnight
6. 6
   기타resulting in a cloudy suspension
7. 7
   기타The solvents are removed under high vacuum
8. 8
   기타does not exceed 50° C.
9. 9
   기타to give a light yellow oil
10. 10
    기타In order to remove traces of pyridine
11. 11
    기타the oil is triturated with toluene
12. 12
    기타again evaporated under high vacuum
13. 13
    workup.DISSOLUTIONThe remaining oil is dissolved in minimum amount of dichloromethane (DCM)
14. 14
    기타purified by flash chromatography (Mobile Phase: DCM/Methanol=96/4 to 88/12 over 24 minutes)

실험 절차

To a solution of Carbobenzyloxy-L-Valine (1.35 g, 5.37 mmol) in anhydrous dichloromethane (12 mL) at 0° C. under argon is added 1-Chloro-N,N,-2-trimethyl-1-propenylamine (848 μL, 6.34 mmol) by dropwise addition via a syringe. The resulting solution is then stirred at 0° C. for 10 minutes resulting in a clear colorless solution. To this solution is then added the N-Acetyl-β-neuraminic Acid Benzyl ester (1-2), previously dissolved in anhydrous pyridine (8.0 mL) via dropwise addition. The solution immediately turns yellow and is kept at 0° C. and under an argon atmosphere for 3 hours. The cooling bath is then removed and the solution kept at rt for overnight resulting in a cloudy suspension. The solvents are removed under high vacuum being careful that the temperature bath does not exceed 50° C. to give a light yellow oil. In order to remove traces of pyridine, the oil is triturated with toluene and again evaporated under high vacuum. The remaining oil is dissolved in minimum amount of dichloromethane (DCM) and loaded directly unto a silica gel column (Silicycle-FLH-R10030B-ISO80, 80 g Cartridge) and purified by flash chromatography (Mobile Phase: DCM/Methanol=96/4 to 88/12 over 24 minutes). Combination of the purest fractions yields 996 mg (32% yield) of pure (1-5) as a white solid. LC/MS: (+) ESI: m/z=633.2 [M+1]; 655.2 [M+Na, major signal); retention time=3.69 min. 1H NMR (400 MHz, d4-MeOD) δ 7.12-7.37 (m, 11H), 5.08-5.17 (m, 2H), 4.95-5.03 (m, 2H), 4.28 (dd, J=11.6, 2.0 Hz, 1H, C-9), 4.18 (dd, J=11.6, 6.0 Hz, 1H, C-9′), 4.05-4.06 (m, 1H), 3.91-3.98 (m, 1H), 3.89 (dd, J=10.5, 1.2 Hz, 1H), 3.80-3.86 (m, 11H), 3.70 (t, 1H), 3.41-3.43 (m, 1H), 2.14 (dd, J=12.8, 4.8 Hz, 1H), 1.98-2.08 (m, 1H), 1.91 (s, 3H), 1.79-1.89 (m, 1H), 0.80-0.84 (m, 6H); 13C NMR (400 mHz, d4-MeOD) δ 173.7, 170.9, 158.9, 136.2, 137.1, 129.6, 129.5, 129.4, 129.1, 129.0, 128.8, 96.7, 72.0, 70.3, 69.3, 68.3, 68.0, 67.8, 61.1, 54.4, 40.7, 32.1, 22.7, 19.6, 18.4.

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