Tetrahydrofuran → (1S,5R,7S,8S)-7-Hydroxy-4-methoxy-8-methyl-8-(4-methyl-4-((triethylsilyl)oxy)pentyl)-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione

HRID 633662Notes

Reaction equation

HRID 633662 reaction equation
C1COCC1.C(=S)(OC1C=CC=CC=1)[O:7][C@H:8]1[CH2:15][C@@:14]2([CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])[C:16](=[O:17])[C@H:10]([C:11](=[O:25])[CH:12]=[C:13]2[O:23][CH3:24])[C@:9]1([CH3:40])[CH2:26][CH2:27][CH2:28][C:29]([CH3:39])([O:31][Si:32]([CH2:37][CH3:38])([CH2:35][CH3:36])[CH2:33][CH3:34])[CH3:30].[Li]N1C(C)(C)CCCC1(C)C.CCCCCC>CCOC(C)=O>[OH:7][C@@H:8]1[C@@:9]([CH3:40])([CH2:26][CH2:27][CH2:28][C:29]([CH3:30])([O:31][Si:32]([CH2:35][CH3:36])([CH2:37][CH3:38])[CH2:33][CH3:34])[CH3:39])[C@@H:10]2[C:16](=[O:17])[C@@:14]([CH2:18][CH:19]=[C:20]([CH3:21])[CH3:22])([C:13]([O:23][CH3:24])=[CH:12][C:11]2=[O:25])[CH2:15]1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8058HexaneHCID 90123985O-((1S,2S,3S,5R)-6-Methoxy-2-methyl-2-(4-methyl-4-((triethylsilyl)oxy)pentyl)-5-(3-methylbut-2-en-1-yl)-8,9-dioxobicyclo[3.3.1]non-6-en-3-yl) O-phenyl carbonothioateHCID 178418821HCID 178418821, compound

Product 1

HCID 71499450(1S,5R,7S,8S)-7-Hydroxy-4-methoxy-8-methyl-8-(4-methyl-4-((triethylsilyl)oxy)pentyl)-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dioneYield 79%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A THF (2 mL) solution of 40 (144 mg, 0.269 mmol, 1 equiv.) was cooled to −78° C. in a 25-mL recovery flask, and a freshly prepared THF solution of lithium tetramethylpiperidide (0.50 M, 2.2 mL, 1.1 mmol, 4 equiv.) was added. The resulting orange solution was stirred at −78° C. for 15 min and then stirred at 0° C. for 40 min. The reaction was then quenched with saturated aqueous NaHCO3 at 0° C. The mixture was warmed to room temperature and extracted thrice with EtOAc. The organic extracts were combined, washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in vacuo to an orange oil. Flash column chromatography (75 mL SiO2, 7:3 hexane:EtOAc) afforded 104.3 mg (0.2117 mmol, 79% yield) of 41 as a faint yellow oil. TLC Rf 0.56 (1:1 hexane:EtOAc). 1H NMR (600 MHz; CDCl3): δ 5.63 (s, 1H), 4.95 (t, J=7.0 Hz, 1H), 3.78 (d, J=7.8 Hz, 1H), 3.73 (s, 3H), 3.15 (s, 1H), 2.47 (dd, J=14.5, 6.4 Hz, 1H), 2.37 (dd, J=14.5, 7.6 Hz, 1H), 2.09 (dd, J=13.4, 5.4 Hz, 1H), 1.88 (s, 1H), 1.73 (dd, J=13.3, 11.6 Hz, 1H), 1.65 (m, 7H), 1.52 (td, J=12.6, 3.5 Hz, 1H), 1.39 (td, J=12.5, 4.1 Hz, 1H), 1.34-1.27 (m, 2H), 1.23 (m, 4H), 1.18 (s, 3H), 0.92 (t, J=7.9 Hz, 9H), 0.86 (s, 3H), 0.54 (q, J=7.8 Hz, 6H). 13C NMR (126 MHz; CDCl3): δ 205.4, 193.1, 177.4, 134.4, 119.0, 105.9, 73.6, 72.0, 69.2, 57.0, 56.0, 46.2, 45.6, 39.4, 38.4, 30.6, 29.50, 29.48, 26.1, 18.1, 17.9, 15.7, 7.3, 6.9. HRMS-ESI (m/z): [M+Na]+ calculated for C28H48O5Si, 515.3163. found, 515.3170.

Workup

  1. stirringstirred at 0° C. for 40 min
  2. customThe reaction was then quenched with saturated aqueous NaHCO3 at 0° C
  3. temperatureThe mixture was warmed to room temperature
  4. extractionextracted thrice with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to an orange oil

Sources & evidence

ORD record
ord-0039f294bba1464395441ef0ac856d90
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

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