(4R)-2-(N,N-diethylamino)methyl-4-(tert-butyldimethylsiloxy)cyclopent-2-en-1-one → (3R,4R)-2-methylene-3-[(3S)-3-(tert-butyldimethylsiloxy)-3-cyclohexylprop-1-ynyl]-4-(tert-butyldimethylsiloxy)cyclopentan-1-one

HRID 2358226Notes

Reaction equation

HRID 2358226 reaction equation
[O:1]([C@@H:9]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[C:10]#[CH:11])[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].C([Li])CCC.[Cl-].C([Al+]CC)C.C(N([CH2:34][C:35]1[C:36](=[O:48])[CH2:37][C@@H:38]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH:39]=1)CC)C>C1(C)C=CC=CC=1.CCCCCC>[CH2:34]=[C:35]1[C@@H:39]([C:11]#[C:10][C@@H:9]([O:1][Si:2]([C:5]([CH3:7])([CH3:8])[CH3:6])([CH3:4])[CH3:3])[CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]2)[C@H:38]([O:40][Si:41]([C:44]([CH3:46])([CH3:45])[CH3:47])([CH3:42])[CH3:43])[CH2:37][C:36]1=[O:48]

Participants

7

Reactant 4

HCID 10424731(4R)-2-(N,N-diethylamino)methyl-4-(tert-butyldimethylsiloxy)cyclopent-2-en-1-oneHCID 11983898(3S)-3-(tert-Butyldimethylsiloxy)-3-cyclohexylprop-1-yneHCID 16686102Diethyl aluminum chlorideHCID 178418339Butyllithium

Product 1

HCID 14844039(3R,4R)-2-methylene-3-[(3S)-3-(tert-butyldimethylsiloxy)-3-cyclohexylprop-1-ynyl]-4-(tert-butyldimethylsiloxy)cyclopentan-1-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent

Procedure

(3S)-3-(tert-Butyldimethylsiloxy)-3-cyclohexylprop-1-yne (6.58 g) was dissolved in toluene (80 ml), and n-butyl lithium (3.0 M, hexane solution, 8.0 ml) was added at 0° C., followed by stirring at the same temperature for 30 minutes. To the solution was added diethylaluminum chloride (0.95 M, hexane solution 29.0 ml) at 0° C., followed by stirring until the solution reached room temperature for 30 minutes. To the solution was added (4R)-2-(N,N-diethylamino)methyl-4-(tert-butyldimethylsiloxy)-cyclopent-2-en-1-one (0.25 M, toluene solution, 80.0 ml) at room temperature, followed by stirring for 15 minutes. The reaction solution, while stirring, was added to a mixture of hexane (190 ml), a saturated aqueous ammonium chloride solution (190 ml) and an aqueous hydrochloric acid solution (3 M, 56 ml), and the organic layer was separated and washed with a saturated aqueous sodium bicarbonate solution (50 ml). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting residue was purified by silica gel column chromatography (developing solvent; hexane:ether=10:1) to give (3R,4R)-2-methylene-3-[(3S)-3-(tert-butyldimethylsiloxy)-3-cyclohexylprop-1-ynyl]-4-(tert-butyldimethylsiloxy)cyclopentan-1-one (7.92 g).

Workup

  1. stirringby stirring until the solution
  2. waitreached room temperature for 30 minutes
  3. stirringby stirring for 15 minutes
  4. stirringThe reaction solution, while stirring
  5. customa saturated aqueous ammonium chloride solution (190 ml) and an aqueous hydrochloric acid solution (3 M, 56 ml), and the organic layer was separated
  6. washwashed with a saturated aqueous sodium bicarbonate solution (50 ml)
  7. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel column chromatography (developing solvent; hexane:ether=10:1)

Sources & evidence

ORD record
ord-355e714a396640d88f193f1b02507d41
Source dataset
uspto-grants-2010_07
Patent number
US07763652B2

Reaction notes

Loading…