Water → 3-Tert-butyldimethylsilylmorphine

HRID 1601625Notes

Reaction equation

HRID 1601625 reaction equation
[CH:1]1[C:17]2[CH2:16][C@H:15]3[N:18]([CH2:20][CH2:21][C@@:7]45[C@H:14]3[CH:13]=[CH:12][C@H:10]([OH:11])[C@@H:8]4[O:9][C:5]([C:6]=25)=[C:3]([OH:4])[CH:2]=1)[CH3:19].C([Li])CCC.[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].O>C1COCC1.C(Cl)Cl.CO>[Si:27]([C:3]1([OH:4])[C:5]2[O:9][C@@H:8]3[C@@:7]45[CH2:21][CH2:20][N:18]([CH3:19])[C@@H:15]([C@@H:14]4[CH:13]=[CH:12][C@@H:10]3[OH:11])[CH2:16][C:17]([C:6]5=2)=[CH:1][CH2:2]1)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 5288826MorphineHCID 178418339Butyllithium

Product 1

HCID 1317199733-Tert-butyldimethylsilylmorphineYield 56.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21226129Dichloromethane methanolSolvent

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%). Recrystallisation from Et2O/petrol (boiling point 40-60°) gave white crystalline needles (1.37 g), m.p.=120-122° C.

Workup

  1. waitThe mixture was left
  2. extractionwas extracted with dichloromethane several times
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customto leave an off-white film

Sources & evidence

ORD record
ord-529a7a063a214c0d9c6efe8955e12b12
Source dataset
uspto-grants-1999_11
Patent number
US05977326

Reaction notes

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