(R)-2-Methyl-CBS-oxazaborolidine → (S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanol

HRID 1922627Notes

Reaction equation

HRID 1922627 reaction equation
[Br:1]/[CH:2]=[C:3]1\[CH2:4][CH2:5][CH2:6][C@@:7]2([CH3:15])[C@H:11]\1[CH2:10][CH:9]=[C:8]2[C:12](=[O:14])[CH3:13].B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@@H]2N1CCC2.CSC.B.[H][H]>C1(C)C=CC=CC=1.O.C(OCC)C.CO>[Br:1]/[CH:2]=[C:3]1\[CH2:4][CH2:5][CH2:6][C@@:7]2([CH3:15])[C@H:11]\1[CH2:10][CH:9]=[C:8]2[C@@H:12]([OH:14])[CH3:13]

Participants

9

Reactant 4

HCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 12423031(Dimethyl sulfide)trihydroboronHCID 594565491-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanone2×HCID 178418361HCID 178418361, compound

Product 1

HCID 59456520(S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanolYield 94.8%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanone (Compound 13: 24.7 mg, 0.0918 mmol) was dissolved in toluene (200 μl), and (R)-2-methyl-CBS-oxazaborolidine (18 μl, 0.018 mmol, 1.0 M in toluene) and borane dimethyl sulfide (26 μl, 0.274 mmol) were added thereto at −20° C., followed by stirring the resulting mixture for 1 hour. Methanol (100 μl) was added to the reaction solution, and when generation of hydrogen gas stopped, diethyl ether and water were added thereto. After separating the organic layer, the aqueous layer was extracted with diethyl ether. The combined organic layer was washed with saturated brine, dried over sodium sulfate, and evaporated. The obtained crude product was purified by flash column chromatography to obtain (S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanol (23.6 mg, 94.8%) as a white solid. The spectrum data thereof agreed with the data described in Example 4.

Workup

  1. customat −20° C.
  2. customAfter separating the organic layer
  3. extractionthe aqueous layer was extracted with diethyl ether
  4. washThe combined organic layer was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe obtained crude product
  8. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-63ed1290be6246758f6148f525954123
Source dataset
uspto-grants-2012_05
Patent number
US08173824B2

Reaction notes

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