Tetrahydrofuran → O-((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 carbonothioate

HRID 633661Notes

Reaction equation

HRID 633661 reaction equation
C1COCC1.[OH:6][C@@H:7]1[C@@:14]([CH3:29])([CH2:15][CH2:16][CH2:17][C:18]([CH3:28])([O:20][Si:21]([CH2:26][CH3:27])([CH2:24][CH3:25])[CH2:22][CH3:23])[CH3:19])[C@@H:13]2[C@:30]([OH:33])(OC)[C@@:9]([CH2:37][CH:38]=[C:39]([CH3:41])[CH3:40])([C:10]([O:35][CH3:36])=[CH:11][C:12]2=[O:34])[CH2:8]1.C([Li])CCC.[CH:47]1[CH:52]=[CH:51][C:50]([O:53][C:54](Cl)=[S:55])=[CH:49][CH:48]=1>CCOC(C)=O.CCCCCC>[C:54](=[S:55])([O:53][C:50]1[CH:51]=[CH:52][CH:47]=[CH:48][CH:49]=1)[O:6][C@H:7]1[CH2:8][C@@:9]2([CH2:37][CH:38]=[C:39]([CH3:41])[CH3:40])[C:30](=[O:33])[C@H:13]([C:12](=[O:34])[CH:11]=[C:10]2[O:35][CH3:36])[C@:14]1([CH3:29])[CH2:15][CH2:16][CH2:17][C:18]([CH3:19])([O:20][Si:21]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:26][CH3:27])[CH3:28]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 70498Phenyl thioxochloroformateHCID 71520048(1S,5R,7S,8S,9S)-7,9-Dihydroxy-4,9-dimethoxy-8-methyl-8-(4-methyl-4-((triethylsilyl)oxy)pentyl)-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-en-2-oneHCID 178418339Butyllithium

Product 1

HCID 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 carbonothioateYield 60%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A THF (2 mL) solution of 39 (71 mg, 0.14 mmol, 1 equiv.) was cooled to −78° C. in a 10-mL recovery flask, and a hexane solution of n-butyllithium (2.02 M, 141 μL, 0.28 mmol, 2.1 equiv.) was added dropwise over 5 min. After stirring the solution at −78° C. for 20 min, O-phenyl chlorothionoformate (39 μL, 0.28 mmol, 2.1 equiv.) was added in one portion. The resulting yellow solution was allowed to slowly warm to room temperature over 90 min and was subsequently quenched at room temperature with saturated aqueous NaHCO3. The mixture was 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 (50 mL SiO2, 95:5 hexane:EtOAc) afforded 51 mg (81 μmol, 60% yield) of 40 as a colorless oil. TLC Rf 0.58 (7:3 hexane:EtOAc). 1H NMR (600 MHz; CDCl3): δ 7.41 (dd, J=8.4, 7.6 Hz, 2H), 7.30 (t, J=7.4 Hz, 1H), 7.08-7.06 (m, 2H), 5.74 (s, 1H), 5.53 (dd, J=11.5, 5.4 Hz, 1H), 4.99 (t, J=7.0 Hz, 1H), 3.80 (s, 3H), 3.25 (s, 1H), 2.56-2.53 (m, 2H), 2.44 (dd, J=14.6, 7.4 Hz, 1H), 1.86 (dd, J=12.9, 11.7 Hz, 1H), 1.69-1.65 (m, 7H), 1.58-1.56 (m, 1H), 1.47-1.41 (m, 2H), 1.37 (m, 2H), 1.23 (s, 3H), 1.23 (s, 3H), 1.03 (s, 3H), 0.95 (t, J=7.9 Hz, 9H), 0.58 (q, J=7.8 Hz, 6H). 13C NMR (126 MHz; CDCl3): δ 204.2, 194.6, 192.2, 177.0, 153.4, 134.9, 129.8, 126.9, 122.0, 118.6, 106.3, 84.6, 73.5, 69.8, 57.3, 55.7, 45.65, 45.58, 38.1, 34.3, 30.5, 29.7, 29.3, 26.1, 18.2, 17.8, 17.5, 7.4, 7.0. HRMS-ESI (m/z): [M+Na]+ calculated for C35H52O6SSi, 651.3152. found, 651.3130.

Workup

  1. temperatureto slowly warm to room temperature over 90 min
  2. customwas subsequently quenched at room temperature with saturated aqueous NaHCO3
  3. extractionThe mixture was extracted thrice with EtOAc
  4. washwashed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to an orange oil

Sources & evidence

ORD record
ord-d2ebd72c8fed4da290cfd6096da18b11
Source dataset
uspto-grants-2016_04
Patent number
US09321713B2

Reaction notes

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