(4S,7R,8S,9S,16S,Z)-4,8-Bis((tert-butyldimethylsilyl)oxy)-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione → Epothilone C

HRID 62562Notes

Reaction equation

HRID 62562 reaction equation
[Si]([O:8][C@@H:9]1[C:24]([CH3:26])([CH3:25])[C:23](=[O:27])[C@H:22]([CH3:28])[C@@H:21]([O:29][Si](C(C)(C)C)(C)C)[C@@H:20]([CH3:37])[CH2:19][CH2:18][CH2:17][CH:16]=[CH:15][CH2:14][C@@H:13](/[C:38](/[CH3:46])=[CH:39]/[C:40]2[N:41]=[C:42]([CH3:45])[S:43][CH:44]=2)[O:12][C:11](=[O:47])[CH2:10]1)(C(C)(C)C)(C)C>C1COCC1.C(Cl)Cl>[CH3:45][C:42]1[S:43][CH:44]=[C:40](/[CH:39]=[C:38](/[C@H:13]2[O:12][C:11](=[O:47])[CH2:10][C@H:9]([OH:8])[C:24]([CH3:26])([CH3:25])[C:23](=[O:27])[C@H:22]([CH3:28])[C@@H:21]([OH:29])[C@@H:20]([CH3:37])[CH2:19][CH2:18][CH2:17][CH:16]=[CH:15][CH2:14]2)\[CH3:46])[N:41]=1

Participants

4

Reactant 1

HCID 11104485(4S,7R,8S,9S,16S,Z)-4,8-Bis((tert-butyldimethylsilyl)oxy)-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione

Product 1

HCID 9891226Epothilone CYield 85.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

A solution of (4S,7R,8S,9S,16S,Z)-4,8-Bis((tert-butyldimethylsilyl)oxy)-5,5,7,9-tetramethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione (26.2 mg, 37.1 μmol) in THF (3.6 ml) in a plastic vial was treated with HF-pyridine complex (70% HF, 1.09 mL). The reaction mixture was stirred at 22° C. for 36 h, diluted with DCM and quenched by NaHCO3 (sat.). The aqueous layer was extracted with DCM (2×). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. Purification on SiO2 (hexanes: diethyl ether 2:1 to 1:1) afforded 15.2 mg (81%, Z:E=95:5) of epothilone C as a colorless solid together with 2.6 mg of mono-desilylated product.

Workup

  1. customquenched by NaHCO3 (sat.)
  2. extractionThe aqueous layer was extracted with DCM (2×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customPurification on SiO2 (hexanes: diethyl ether 2:1 to 1:1)

Sources & evidence

ORD record
ord-bd750b52a05f4bdf863c24faf48bf094
Source dataset
uspto-grants-2016_09
Patent number
US09446394B2

Reaction notes

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