Lithium naphthalenide → (1R*,2R*,5R*)-8-Benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol

HRID 2088097

Reaction equation

HRID 2088097 reaction equation
[C-]1C2C(=CC=CC=2)C=CC=1.[Li+].[CH2:12]([N:19]1[C@@H:24]2[C@H:25](S(C3C=CC=CC=3)(=O)=O)[CH2:26][C@@:20]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:21]([OH:36])[CH2:22][CH2:23]2)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1COCC1>[CH2:12]([N:19]1[C@@H:24]2[CH2:25][CH2:26][C@@:20]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:21]([OH:36])[CH2:22][CH2:23]2)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 11768624Lithium naphthalenideHCID 69890353(1R*,2R*,5S*,6R*)-8-Benzyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-ol

Product 1

HCID 69688994(1R*,2R*,5R*)-8-Benzyl-1-phenyl-8-azabicyclo[3.2.1]octan-2-olYield 84.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium naphthalenide (200 ml, 0.6M in teterahydrofuran) was added dropwise into a −78° C. solution of (1R*,2R*,5S*,6R*)-8-benzyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-ol (Description 4; 25 g, 57.7 mmol) in THF (350 ml). The mixture was quenched by addition of saturated ammonium chloride and warmed to room temperature The reaction mixture was partitioned between ethyl acetate and saturated ammonium chloride. The organic layer was washed (×2) with water then dried (MgSO4), filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 5, 15 and 40% ethyl acetate/iso-hexanes to yield the title compound (14.3 g, 84.6%).

Workup

  1. customThe mixture was quenched by addition of saturated ammonium chloride
  2. customwas partitioned between ethyl acetate and saturated ammonium chloride
  3. washThe organic layer was washed (×2) with water
  4. dry with materialthen dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed on silica gel eluting with 5, 15 and 40% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-161e92622f60454e9cc151d3e58bf2c2
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Linked notes

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