Dimethyl Sulfoxide → (4bS,8R,8aS,9aR,10S,13aR,13bR)-10-tert-butyl-7-cyclopropylmethyl-5,6,7,8,9,9a,10,13b-octahydro-10-methyl-8a,13a-ethano-4,8-methanobenzofuro[3,2-e][1,3]dioxino[4,5-g]isoquinolin-1-ol

HRID 629829Notes

Reaction equation

HRID 629829 reaction equation
CS(C)=O.[CH3:5][Si](Cl)(C)C.[CH:10]1([CH2:13][N:14]2[CH2:34][CH2:33][C@@:21]34[C:22]5[C:27]6[CH2:28][C@@H:15]2[C@H:16]3[CH2:17][C@H:18]([C@:36]([OH:42])([C:38]([CH3:41])([CH3:40])[CH3:39])[CH3:37])[C@H:19]([OH:35])[C@@H:20]4[O:32][C:23]=5[C:24]([OH:31])=[C:25]2CC[C:26]2=6)[CH2:12][CH2:11]1.[CH2:43]1COC[CH2:44]1>>[C:38]([C@:36]1([CH3:37])[C@@H:18]2[C@@:19]3([CH2:44][CH2:43][C@:16]4([CH2:17]2)[C@@:21]25[C:22]6[C:27](=[CH:26][CH:25]=[C:24]([OH:31])[C:23]=6[O:32][C@@H:20]32)[CH2:28][C@H:15]4[N:14]([CH2:13][CH:10]2[CH2:11][CH2:12]2)[CH2:34][CH2:33]5)[O:35][CH2:5][O:42]1)([CH3:39])([CH3:41])[CH3:40]

Participants

5

Reactant 4

HCID 679Dimethyl SulfoxideHCID 6397ChlorotrimethylsilaneHCID 8028Tetrahydrofuran2×HCID 8671165917-cyclopropylmethyl-7alpha-[(2S)-3,3-dimethyl-2-hydroxybutan-2-yl]-4,5alpha-epoxy-3,6-dihydroxy-6alpha,14alpha-ethanomorphinan

Product 1

HCID 73211769(4bS,8R,8aS,9aR,10S,13aR,13bR)-10-tert-butyl-7-cyclopropylmethyl-5,6,7,8,9,9a,10,13b-octahydro-10-methyl-8a,13a-ethano-4,8-methanobenzofuro[3,2-e][1,3]dioxino[4,5-g]isoquinolin-1-olYield 34.4%

Procedure

To a solution of DMSO (2.1 ml, 28.7 mMol) in THF (10 ml), at ambient temperature, was added trimethylsilyl chloride (TMSCl) (2.7 ml, 20.8 mMol). After 30 minute agitation, a solution of compound 2 (1.5 g, 3.3 mMol) in THF (12.5 ml) was added and the mixture was stirred at ambient temperature. After 24 h reaction time at ambient temperature, the reaction conversion was about 85% at which point the reaction was quenched by addition of saturated aqueous NaHCO3 solution (100 ml). The resulting mixture was extracted with EtOAc (2×100 ml). The combined organic extracts were dried over MgSO4, filtered, and concentrated to give 2.7 g of crude product. After purification by column chromatography on silica gel, 0.52 g of the title compound 3 (34.4% yield) was obtained with a purity of >99%.

Workup

  1. customAfter 24 h reaction time at ambient temperature
  2. customwas quenched by addition of saturated aqueous NaHCO3 solution (100 ml)
  3. extractionThe resulting mixture was extracted with EtOAc (2×100 ml)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give 2.7 g of crude product
  8. customAfter purification by column chromatography on silica gel

Sources & evidence

ORD record
ord-b632b23af3994629b255429180e391c8
Source dataset
uspto-grants-2016_04
Patent number
US09315514B2

Reaction notes

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