Cerium(III) chloride → (1R*,2S*,5S*,6R*)-8-Benzyl-2-(2-cyclopropyloxy-5-trifluoromethoxyphenyl)ethynyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-ol

HRID 1017262Notes

Reaction equation

HRID 1017262 reaction equation
C([Li])CCC.[CH:6]1([O:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][C:11]=2[C:21]#[CH:22])[CH2:8][CH2:7]1.[Cl-].[Ce+3].[Cl-].[Cl-].[CH2:27]([N:34]1[C@@H:39]2[C@H:40]([S:42]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)(=[O:44])=[O:43])[CH2:41][C@@:35]1([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C:36](=[O:51])[CH2:37][CH2:38]2)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O1CCCC1>[CH2:27]([N:34]1[C@@H:39]2[C@H:40]([S:42]([C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)(=[O:43])=[O:44])[CH2:41][C@@:35]1([C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[C@:36]([C:22]#[C:21][C:11]1[CH:12]=[C:13]([O:16][C:17]([F:18])([F:19])[F:20])[CH:14]=[CH:15][C:10]=1[O:9][CH:6]1[CH2:7][CH2:8]1)([OH:51])[CH2:37][CH2:38]2)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 24636Cerium(III) chlorideHCID 112765472-Cyclopropyloxy-5-trifluoromethoxyphenylethyneHCID 69889408(1R*,5S*,6R*)-8-Benzyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-oneHCID 178418339Butyllithium

Product 1

HCID 70152611(1R*,2S*,5S*,6R*)-8-Benzyl-2-(2-cyclopropyloxy-5-trifluoromethoxyphenyl)ethynyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-olYield 53.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of n-butyl lithium in hexanes (1.6M, 5 ml, 8 mmol) was added dropwise to a stirred solution of 2-cyclopropyloxy-5-trifluoromethoxyphenylethyne (Description 4; 2.0 g, 8.2 mmol) in tetrahydrofuran (30 ml) at −78° C. to form an orange solution that turned violet at the end of addition. The mixture was stirred for 10 minutes and solid anhydrous cerium(III) chloride (2 g, 8.1 mmol) was added. The mixture was stirred for 30 minutes at −78° C. and a solution of (1R*,5S*,6R*)-8-benzyl-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-one (Description 7; 2.9 g, 6.7 mmol) in tetrahydrofuran (25 ml) was added dropwise. The reaction mixture was warmed to 0° C. over 30 minutes, stirred at 0° C. for 15 minutes, quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (3×100 ml). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate) to give the title compound (2.4 g, 53%) which was recrystallised from ethyl acetate:iso-hexane.

Workup

  1. customto form an orange solution that
  2. additionturned violet at the end of addition
  3. stirringThe mixture was stirred for 30 minutes at −78° C.
  4. stirringstirred at 0° C. for 15 minutes
  5. customquenched with saturated aqueous ammonium chloride
  6. extractionextracted with ethyl acetate (3×100 ml)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-93c54564cb914c8caf34b021553ccda8
Source dataset
uspto-grants-2002_11
Patent number
US06479486B2

Reaction notes

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