Lithium Chloride → (1R*,2R*,5S*,6R*)-8-Benzyl-2',5'-dihydro-4'-(2-methoxy-5-trifluoromethoxyphenyl)-1-phenyl-6-phenylsulfonylspiro[8-azabicyclo[3.2.1]octane-2,2'-furan]

HRID 1017278Notes

Reaction equation

HRID 1017278 reaction equation
[CH2:1]([N:8]1[C@H:12]2[CH2:13][CH2:14][C@@:15]3([CH:19]=[C:18]([Sn](CCCC)(CCCC)CCCC)[CH2:17][O:16]3)[C@:9]1([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[CH2:10][C@H:11]2[S:33]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)(=[O:35])=[O:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Li+].[CH3:50][O:51][C:52]1[CH:57]=[CH:56][C:55]([O:58][C:59]([F:62])([F:61])[F:60])=[CH:54][C:53]=1I>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[CH2:1]([N:8]1[C@H:12]2[CH2:13][CH2:14][C@@:15]3([CH:19]=[C:18]([C:53]4[CH:54]=[C:55]([O:58][C:59]([F:62])([F:61])[F:60])[CH:56]=[CH:57][C:52]=4[O:51][CH3:50])[CH2:17][O:16]3)[C@:9]1([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[CH2:10][C@H:11]2[S:33]([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)(=[O:34])=[O:35])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 433294Lithium ChlorideHCID 184034102-Methoxy-5-trifluoromethoxyiodobenzeneHCID 70160343(1R*,2R*,5S*,6R*)-8-Benzyl-2',5'-dihydro-1-phenyl-6-phenylsulfonyl-4'-tributylstannylspiro[8-azabicyclo[3.2.1]octane-2,2'-furan]

Product 1

HCID 70152121(1R*,2R*,5S*,6R*)-8-Benzyl-2',5'-dihydro-4'-(2-methoxy-5-trifluoromethoxyphenyl)-1-phenyl-6-phenylsulfonylspiro[8-azabicyclo[3.2.1]octane-2,2'-furan]Yield 87%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Tetrakis(triphenylphosphine) palladium(0) (20 mg, 0,017 mmol) was added to a degassed suspension of (1R*,2R*,5S*,6R*)-8-Benzyl-2′,5′-dihydro-1-phenyl-6-phenylsulfonyl-4′-tributylstannylspiro[8-azabicyclo[3.2.1]octane-2,2′-furan](Description 18; 150 mg, 0.2 mmol), lithium chloride (50 mg, 1.2 mmol), 2-methoxy-5-trifluoromethoxyiodobenzene (100 mg, 0.3 mmol) and copper(I) iodide (10 mg, 0.05 mmol) in toluene (10 ml). The mixture was heated to reflux for 18 hours. On cooling the mixture was diluted with ethyl acetate (50 ml) and filtered through Celite™. The filtrate was washed with water (25 ml) then dried (MgSO4), filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 10, 20 and 30% ethyl acetate/iso-hexanes to give the title compound (115 mg, 87%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 hours
  3. temperatureOn cooling the mixture
  4. filtrationfiltered through Celite™
  5. washThe filtrate was washed with water (25 ml)
  6. dry with materialthen dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was chromatographed on silica gel eluting with 10, 20 and 30% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-816805bb4c1749268f2a9abb917dff53
Source dataset
uspto-grants-2002_11
Patent number
US06479486B2

Reaction notes

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