7,13-Diacetylbaccatin III → 2-Debenzoyl-7,13-diacetylbaccatin III

HRID 859837Notes

Reaction equation

HRID 859837 reaction equation
[H-].COCCO[Al+]OCCOC.[CH3:13][C:14]1[C@@H:31]([O:32][C:33]([CH3:35])=[O:34])[CH2:30][C@:26]2([OH:36])[C:27]([CH3:29])([CH3:28])[C:15]=1[C@@H:16]([O:57][C:58]([CH3:60])=[O:59])[C:17]([C@@:19]1([CH3:56])[C@H:24]([C@@H:25]2[O:37]C(C2C=CC=CC=2)=O)[C@:23]2([O:48][C:49]([CH3:51])=[O:50])[CH2:46][O:47][C@@H:22]2[CH2:21][C@@H:20]1[O:52][C:53]([CH3:55])=[O:54])=[O:18]>C1COCC1>[CH3:13][C:14]1[C@@H:31]([O:32][C:33]([CH3:35])=[O:34])[CH2:30][C@:26]2([OH:36])[C:27]([CH3:28])([CH3:29])[C:15]=1[C@@H:16]([O:57][C:58]([CH3:60])=[O:59])[C:17]([C@@:19]1([CH3:56])[C@H:24]([C@@H:25]2[OH:37])[C@:23]2([O:48][C:49]([CH3:51])=[O:50])[CH2:46][O:47][C@@H:22]2[CH2:21][C@@H:20]1[O:52][C:53]([CH3:55])=[O:54])=[O:18]

Participants

4

Reactant 2

HCID 109743987,13-Diacetylbaccatin IIIHCID 22591236HCID 22591236, compound

Product 1

HCID 1010996262-Debenzoyl-7,13-diacetylbaccatin IIIYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Bis(2-methoxyethoxy)-aluminum hydride (65+ wt % in toluene, 3 equiv.) was added dropwise to a stirred solution of 7,13-diacetylbaccatin III (170 mg, 253 μmol) in dry THF (2 mL) at 0° C. After stirring for 30 minutes at 0° C., the reaction was quenched by dropwise addition of saturated NH4Cl. The mixture was stirred for 10 minutes, then warmed to room temperature and diluted with EtOAc (50 mL), followed by addition of water (10 mL). The aqueous phase was separated and extracted again with EtOAc (2×25 mL). The combined organic fractions were washed with brine and water, then dried over anhydrous MgSO4. The solvent was evaporated and the crude product was purified by silica gel flash column chromatography (40–60% EtOAc gradient in hexane) to yield 2-debenzoyl-7,13-diacetylbaccatin III (see FIG. 11) (60 mg, 42% yield, 99% purity by 1H-NMR). 1H-NMR (300 MHz, CDCl3)δ: 1.04 (s, CH3), 1.22 (s, CH3), 1.77 (s, CH3), 1.85 (ddd, J=1.8, 10.8, and 14.4 Hz, H-6β), 1.90 (d, J=1.2 Hz, vinyl-CH3), 2.02 (s, C(O)CH3), 2.14 (s, C(O)CH3), 2.15 (s, C(O)CH3), 2.20 (s, C(O)CH3), 2.58 (ddd, J=7.2, 9.6, and 14.4 Hz, H-6α), 2.65 (d, J=5.1 Hz, OH at C-2), 3.58 (d, J=6.9 Hz, H-3), 3.90 (dd, J=5.4 and 6.5 Hz, H-2), 4.49 (d, J=9.6 Hz, H-20α), 4.63 (d, J=9.6 Hz, H-20β), 4.97 (dd, J=1.8 and 9.6 Hz, H-5), 5.55 (dd, J=7.2 and 10.7 Hz, H-7), 6.15 (dt, J=1.2 and 9.6 Hz, H-13), 6.18 (s, H-10), H-14 proton signal obscured. APCI-MS: m/z 567 (PH+)

Workup

  1. customthe reaction was quenched by dropwise addition of saturated NH4Cl
  2. stirringThe mixture was stirred for 10 minutes
  3. temperaturewarmed to room temperature
  4. additiondiluted with EtOAc (50 mL)
  5. additionfollowed by addition of water (10 mL)
  6. customThe aqueous phase was separated
  7. extractionextracted again with EtOAc (2×25 mL)
  8. washThe combined organic fractions were washed with brine and water
  9. dry with materialdried over anhydrous MgSO4
  10. customThe solvent was evaporated
  11. customthe crude product was purified by silica gel flash column chromatography (40–60% EtOAc gradient in hexane)

Sources & evidence

ORD record
ord-f8de524c9c714efe9ef4c12971fa0fda
Source dataset
uspto-grants-2006_12
Patent number
US07153676B1

Reaction notes

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