Hydrochloric Acid → (3r,4r)-2-Methylene-3-[(3s)-3-tert-butyldimethylsiloxy-5-phenylpent-1-ynyl]-4-(tert-butyldimethylsiloxy)cyclopentan-1-one

HRID 1018818Notes

Reaction equation

HRID 1018818 reaction equation
[O:1]([C@@H:9]([CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=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([CH2:36][C:37]1[C:38](=[O:50])[CH2:39][C@@H:40]([O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44])[CH:41]=1)CC)C.[Cl-].[NH4+].Cl>CCCCCC.C1(C)C=CC=CC=1>[CH2:36]=[C:37]1[C@@H:41]([C:11]#[C:10][C@@H:9]([O:1][Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3])[CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@H:40]([O:42][Si:43]([C:46]([CH3:48])([CH3:47])[CH3:49])([CH3:44])[CH3:45])[CH2:39][C:38]1=[O:50]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 10424731(4R)-2-(N,N-diethylamino)methyl-4-(tert-butyldimethylsiloxy)cyclopent-2-en-1-oneHCID 16686102Diethyl aluminum chlorideHCID 25257491(3s)-3-(Tert-butyldimethylsiloxy)-5-phenyl-1-pentyneHCID 178418339Butyllithium

Product 1

HCID 22899370(3r,4r)-2-Methylene-3-[(3s)-3-tert-butyldimethylsiloxy-5-phenylpent-1-ynyl]-4-(tert-butyldimethylsiloxy)cyclopentan-1-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent

Procedure

To a toluene solution (22 ml) of (3S)-3-(tert-butyldimethylsiloxy)-5-phenyl-1-pentyne (1.96 g) was added n-butyl lithium (2.5 M, hexane solution, 2.64 ml) at 0° C., followed by stirring at room temperature for 30 minutes. To the solution was added diethylaluminum chloride (0.95 N, hexane solution, 8.10 ml) at 0° C., followed by stirring at 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, 22.0 ml) at room temperature, followed by stirring for 15 minutes. The reaction solution was poured into a mixture of hexane (53 ml), a saturated aqueous ammonium chloride solution (53 ml) and an aqueous hydrochloric acid solution (3 N, 15.4 ml) with stirring, and the organic layer was separated and washed with a saturated aqueous sodium bicarbonate solution (20 ml). The resulting organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated, and the resulting residue was purified by a silica gel column chromatography (developing solvent; hexane:ethyl acetate=49:1) to give (3R,4R)-2-methylene-3-[(3S)-3-tert-butyldimethylsiloxy-5-phenylpent-1-ynyl]-4-(tert-butyldimethylsiloxy)cyclopentan-1-one (1.65 g).

Workup

  1. stirringby stirring at room temperature for 30 minutes
  2. stirringby stirring for 15 minutes
  3. customthe organic layer was separated
  4. washwashed with a saturated aqueous sodium bicarbonate solution (20 ml)
  5. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe resulting residue was purified by a silica gel column chromatography (developing solvent; hexane:ethyl acetate=49:1)

Sources & evidence

ORD record
ord-db6113cb0c6d488faafe8ddc68c13392
Source dataset
uspto-grants-2002_11
Patent number
US06482990B1

Reaction notes

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