Silane, trimethyl(2-propyn-1-yloxy)- → (1R*,2R*,5S*,6R*)-8-benzyl-2-(3-hydroxypropynyl)-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-ol

HRID 1017264Notes

Reaction equation

HRID 1017264 reaction equation
C([Li])CCC.C[Si]([O:10][CH2:11][C:12]#[CH:13])(C)C.[CH2:14]([N:21]1[C@@H:26]2[C@H:27]([S:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH2:28][C@@:22]1([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:23](=[O:38])[CH2:24][CH2:25]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O1CCCC1>[CH2:14]([N:21]1[C@@H:26]2[C@H:27]([S:29]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)(=[O:30])=[O:31])[CH2:28][C@@:22]1([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C@@:23]([C:13]#[C:12][CH2:11][OH:10])([OH:38])[CH2:24][CH2:25]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 79696Silane, trimethyl(2-propyn-1-yloxy)-HCID 69889408(1R*,5S*,6R*)-8-Benzyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-oneHCID 178418339Butyllithium

Product 1

HCID 70152384(1R*,2R*,5S*,6R*)-8-benzyl-2-(3-hydroxypropynyl)-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-olYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-butyl lithium in hexanes (1.6M, 20 ml, 32 mmol) was added to a stirred, −78° C. solution of O-trimethylsilylpropargyl alcohol (5 ml, 34.8 mmol) in tetrahydrofuran (50 ml). After 30 minutes a solution of (1R*,5S*,6R*)-8-benzyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-one (Description 7; 4.6 g, 10.7 mmol) in tetrahydrofuran (20 ml) was added. The mixture was stirred for 30 minutes then quenched by addition of saturated ammonium chloride. The mixture was diluted with ethyl acetate and washed (2×100 ml) with water. The organic layer was separated and treated with a solution of tetrabutylammonium fluoride (11.5 ml, 1.0M solution in tetrahydrofuran) for 20 minutes at room temperature. The solution was washed with water (2×100 ml) then dried (MgSO4), filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 1:1, 3:2 and 2:1 ethyl acetate/iso-hexanes to yield the title compound (4.12 g, 79%).

Workup

  1. customthen quenched by addition of saturated ammonium chloride
  2. additionThe mixture was diluted with ethyl acetate
  3. washwashed (2×100 ml) with water
  4. customThe organic layer was separated
  5. additiontreated with a solution of tetrabutylammonium fluoride (11.5 ml, 1.0M solution in tetrahydrofuran) for 20 minutes at room temperature
  6. washThe solution was washed with water (2×100 ml)
  7. dry with materialthen dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was chromatographed on silica gel eluting with 1:1, 3:2 and 2:1 ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-b9936eff42334c789a98687628483200
Source dataset
uspto-grants-2002_11
Patent number
US06479486B2

Reaction notes

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