Dimethyl Sulfoxide → (1R,2R,4R,5S)-4-bromo-2-(2-bromophenyl)-6-oxabicyclo[3.2.1]octan-7-one

HRID 750785Notes

Reaction equation

HRID 750785 reaction equation
Br[Si](C)(C)C.CS(C)=O.[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C@H:17]1[C@H:22]([C:23]([OH:25])=[O:24])[CH2:21][CH:20]=[CH:19][CH2:18]1.C=CC=C.[Br:30]C1C=CC=CC=1C=CC(O)=O.C(N(C(C)C)CC)(C)C>C(Cl)(Cl)Cl.C(OCC)(=O)C>[Br:30][C@H:19]1[C@@H:20]2[CH2:21][C@@H:22]([C:23](=[O:25])[O:24]2)[C@H:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[Br:10])[CH2:18]1

Participants

9

Reactant 6

HCID 679Dimethyl SulfoxideHCID 78451,3-ButadieneHCID 76113BromotrimethylsilaneHCID 81531DiisopropylethylamineHCID 1013463-(2-Bromophenyl)prop-2-enoic acidHCID 11495061(-)-(1R,6R)-6-(2-bromophenyl)cyclohex-3-ene-1-carboxylic acid

Product 1

HCID 11667632(1R,2R,4R,5S)-4-bromo-2-(2-bromophenyl)-6-oxabicyclo[3.2.1]octan-7-one

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Bromotrimethylsilane (1.96 mL, 15.1 mmol) was added dropwise to a 0° C. solution of dimethyl sulfoxide (1.10 mL, 15.5 mmol) in chloroform (15 mL) with stirring at this temperature for 30 minutes. (−)-(1R,6R)-6-(2-bromophenyl)cyclohex-3-ene-1-carboxylic acid (4.24 g, 15.1 mmol; prepared in 93% ee, [α]D=62° (c=1.0, CHCl3), by resolution of the racemic Diels-Alder adduct between 1,3-butadiene and 2-bromocinnamic acid [see Morn, R.; Manuel, C.; Mazmanian, C. Eur. J. Med. Chem. 1976, 11, 493-499]with (R)-phenethyl amine) was added as a solid with stirring at rt for 1 h prior to the addition of diisopropylethylamine (2.65 mL, 15.2 mmol) at 0° C. followed by reflux for 24 hours. The reaction vessel contents were then cooled to rt, diluted with ethyl acetate and washed in succession with water, 5% HCl, water and brine, and the organic phase was dried over sodium sulfate. Concentration in vacuo afforded (1R,2R,4R,5S)-4-bromo-2-(2-bromophenyl)-6-oxabicyclo[3.2.1]octan-7-one as an oily solid.

Workup

  1. stirringwith stirring at rt for 1 h
  2. temperatureby reflux for 24 hours
  3. washwashed in succession with water, 5% HCl, water and brine
  4. dry with materialthe organic phase was dried over sodium sulfate
  5. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-902e252624014adf8a1c06b8c5573374
Source dataset
uspto-grants-2008_07
Patent number
US07405229B2

Reaction notes

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