Reaction #82146

ord-f0700bf557b44f22a9ba3a8c2632d415

Reaction equation

O
Water
[Li][CH2]CCC
butyllithium
CN1CC[C@]23c4c5ccc(O)c4O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1C5
morphine
CC(C)(C)[Si](C)(C)Cl
TBDMS chloride
→
CN1CC[C@]23C4=C5O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1CC4=CCC5(O)[Si](C)(C)C(C)(C)C
product
Yield 56.1%
CN1CC[C@]23C4=C5O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1CC4=CCC5(O)[Si](C)(C)C(C)(C)C
3-tert-butyldimethylsilylmorphine
Yield 56.1%

Reactants

O
Water
[Li][CH2]CCC
butyllithium
CN1CC[C@]23c4c5ccc(O)c4O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1C5
morphine
CC(C)(C)[Si](C)(C)Cl
TBDMS chloride

Reagents

None

Solvents

CO.ClCCl
CH2Cl2 MeOH
C1CCOC1
THF
C1CCOC1
THF

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.WAITThe mixture was left
  2. 2
    Extractionwas extracted with dichloromethane several times
  3. 3
    Washwashed with brine
  4. 4
    Dryingdried over Na2SO4
  5. 5
    Filtrationfiltered
  6. 6
    Otherthe solvent removed in vacuo
  7. 7
    Otherto leave an off-white film

Procedure

To a stirred suspension of anhydrous morphine (7.01 mmol) at -78° C. in anhydrous THF (15 ml) was added 1.6M butyllithium (4.8 ml, 0.492 g, 7.68 mmol) over 8 minutes. 42 minutes later, a solution of TBDMS chloride (1.27 g, 8.43 mmol) in anhydrous THF (10 ml) was added over 10 minutes. The mixture was left to warm up gradually to room temperature overnight by which time all the material had gone into solution. Water was then added to the mixture which was extracted with dichloromethane several times. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered and the solvent removed in vacuo to leave an off-white film. Chromatography over silica using CH2Cl2 /MeOH (5:1) as eluent afforded the product as a white solid (1.58 g, 56%). Recrystallization from Et2O/petrol (boiling point 40°-60°) gave white crystalline needles (1.37 g), m.p.=120°-122° C.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05621087uspto-grants-1997_04