Triethylamine → (1R*,2R*,4'S*,5S*,6R*)-8-Benzyl-4'-(2-benzyloxy-5-trifluoromethoxyphenyl)-2',3',4',5'-tetrahydro-1-phenyl-6-phenylsulfonylspiro[8-azabicyclo[3.2.1]octane-2,2'-furan]

HRID 1017266Notes

Reaction equation

HRID 1017266 reaction equation
[CH2:1]([N:8]1[C@H:12]2[CH2:13][CH2:14][C@@:15]3([CH:19]=[CH:18][CH2:17][O:16]3)[C@:9]1([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:10][C@H:11]2[S:20]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=[O:22])=[O:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:35]([O:42][C:43]1[CH:48]=[CH:47][C:46]([O:49][C:50]([F:53])([F:52])[F:51])=[CH:45][C:44]=1I)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[Cl-].[Li+].C(N(CC)CC)C.C([O-])=O.[K+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CN(C)C=O>[CH2:1]([N:8]1[C@H:12]2[CH2:13][CH2:14][C@@:15]3([CH2:19][C@@H:18]([C:44]4[CH:45]=[C:46]([O:49][C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:48][C:43]=4[O:42][CH2:35][C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[CH2:17][O:16]3)[C@:9]1([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:10][C@H:11]2[S:20]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)(=[O:21])=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 433294Lithium ChlorideHCID 2735122Potassium FormateHCID 113952781-(Benzyloxy)-2-iodo-4-(trifluoromethoxy)benzeneHCID 70152619(1R*,2R*,5S*,6R*)-8-benzyl-1-phenyl-6-phenylsulphonylspiro[8-azabicyclo[3.2.1]octane-2,2'(5'H)-furan]

Product 1

HCID 70153087(1R*,2R*,4'S*,5S*,6R*)-8-Benzyl-4'-(2-benzyloxy-5-trifluoromethoxyphenyl)-2',3',4',5'-tetrahydro-1-phenyl-6-phenylsulfonylspiro[8-azabicyclo[3.2.1]octane-2,2'-furan]Yield 44%

Reagents, catalysts & solvents 4

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Palladium acetate (140 mg, 0.6 mmol) was added to a degassed suspension of (1R*,2R*,5S*,6R*)-8-benzyl-2′,5′-dihydro-1-phenyl-6-phenylsulfonylspiro[8-azabicyclo[3.2.1]octane-2,2′-furan] (Description 15; 2.9 g, 6.15 mmol), 2-benzyloxy-5-trifluoromethoxyiodobenzene (7.3 g, 18.5 mmol), tetrabutylammonium chloride, (1.7 g, 6.15 mmol), lithium chloride (2.6 g, 62 mmol), triethylamine (2.6 ml, 18 mmol), potassium formate (1.56 g, 18.5 mmol), N,N-dimethylformamide (40 ml) and water (3 ml). The mixture was stirred at 60° C. for 72 hours then partitioned between brine and ethyl acetate. The organic layer was washed (×3) with water then dried (MgSO4), filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 5, 10, 15 and 30% ethyl acetate/iso-hexanes to yield the title compound (2.0 g, 44%).

Workup

  1. customthen partitioned between brine and ethyl acetate
  2. washThe organic layer was washed (×3) with water
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel eluting with 5, 10, 15 and 30% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-8ef3c5e467f04eec90823d2b36d21515
Source dataset
uspto-grants-2002_11
Patent number
US06479486B2

Reaction notes

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