反応 #164435

反応方程式

N-Acetyl-β-neuraminic Acid Benzyl ester

Carbobenzyloxy-L-Valine

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

→

( 1-5 )

収率 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

収率 32.0%

溶媒

pyridine

dichloromethane

反応条件

後処理

1. 1
   workup.ADDITIONby dropwise addition via a syringe
2. 2
   その他resulting 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
   その他The cooling bath is then removed
5. 5
   workup.WAITthe solution kept at rt for overnight
6. 6
   その他resulting in a cloudy suspension
7. 7
   その他The solvents are removed under high vacuum
8. 8
   その他does not exceed 50° C.
9. 9
   その他to give a light yellow oil
10. 10
    その他In order to remove traces of pyridine
11. 11
    その他the oil is triturated with toluene
12. 12
    その他again evaporated under high vacuum
13. 13
    workup.DISSOLUTIONThe remaining oil is dissolved in minimum amount of dichloromethane (DCM)
14. 14
    その他purified by flash chromatography (Mobile Phase: DCM/Methanol=96/4 to 88/12 over 24 minutes)

実験手順

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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