Reaction #90247

Reaction equation

8

(R)-benzyl 4-(((2R,3R,5R,6S)-5-(((R)-3-azido-2-methylpropanoyl)oxy)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoate

10

5-(((2R,3R,5R,6S)-3,5-bis(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoic acid

EDC hydrochloride

ethyl acetate

→

(2R,3R,5R,6S)-5-(((R)-3-azido-2-methylpropanoyl)oxy)-2-(((R)-5-(benzyloxy)-5-oxopentan-2-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl 5-(((2R,3R,5R,6S)-3,5-bis(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoate

Yield 97.0%

Solvents

dichloromethane

hexane

Conditions

Workup

1. 1
   OtherTo prepare 40
2. 2
   Otherwas quenched by addition of 5% aqueous acetic acid (50 μl)
3. 3
   Dryingdried over Na2SO4
4. 4
   Concentrationconcentrated in vacuo

Procedure

To prepare 40, a solution of 8 (5.2 mg, 11.6 μmol) and 10 (6.4 mg, 14.9 μmol) in 1 mL dichloromethane was treated with 4-dimethylaminopyridine (3.7 mg, 30 μmol) and EDC hydrochloride (5.8 mg, 30 μmol). After stirring at room temperature for 12 hours the reaction was quenched by addition of 5% aqueous acetic acid (50 μl), dried over Na2SO4, and concentrated in vacuo. Flash column chromatography on silica using a gradient of 0-50% ethyl acetate in hexane afforded (2R,3R,5R,6S)-5-(((R)-3-azido-2-methylpropanoyl)oxy)-2-(((R)-5-(benzyloxy)-5-oxopentan-2-yl)oxy)-6-methyltetrahydro-2H-pyran-3-yl 5-(((2R,3R,5R,6S)-3,5-bis(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)oxy)pentanoate (40) (9.6 mg, 11.2 μmol, 97%) as a colorless oil. 1H NMR (500 MHz, acetone-d6): δ (ppm) 7.40-7.25 (m, 15H), 5.15 (d, J=12.3 Hz, 1H), 5.12 (d, J=12.3 Hz, 1H), 4.84-4.78 (m, 2H), 4.66 (s, 1H), 4.74 (s, 1H), 4.58 (d, J=12.3 Hz, 1H), 4.57 (d, J=11.4 Hz, 1H), 4.53 (d, J=12.3 Hz, 1H), 4.46 (d, J=11.4 Hz, 1H), 3.87-3.80 (m, 2H), 3.75-3.67 (m, 2H), 3.60-3.56 (m, 1H), 3.51 (dd, J=12.2 Hz, 7.6 Hz, 1H), 3.47-3.34 (m, 3H), 2.68-2.60 (m, 1H), 2.55-2.41 (m, 2H), 2.38 (t, J=7.4 Hz, 2H), 2.24-2.18 (m, 1H), 2.12-2.06 (m, 1H), 1.96-1.85 (m, 3H), 1.77-1.65 (m, 3H), 1.64-1.55 (m, 2H), 1.29 (d, J=6.2 Hz, 3H), 1.19 (d, J=7.1 Hz, 3H), 1.16 (d, J=6.2 Hz, 3H), 1.15 (d, J=6.1 Hz, 3H). 13C NMR (125 MHz, acetone-d6): δ (ppm) 173.4, 173.2, 172.9, 138.6, 138.5, 136.0, 128.7, 128.52, 128.51, 128.45, 128.38, 128.0, 127.79, 127.77, 97.2, 93.5, 75.6, 75.4, 71.4, 71.24, 71.22, 70.5, 70.4, 68.3, 67.0, 66.8, 66.5, 55.8, 40.1, 34.1, 32.1, 30.6, 29.9, 29.7, 29.5, 29.1, 21.8, 18.9, 18.3, 17.7, 14.9. ESI+ MS: m/z=882.5 [M+Na+] and 898.5 [M+K+]. See FIGS. 107A-B.

Source