Methyl iodide → HCID 86586763, compound

HRID 2088214Notes

Reaction equation

HRID 2088214 reaction equation
I[CH3:2].[CH2:3]([N:10]1[C@@H:15]2[C@H:16]([C:18]3[N:19]=[N:20][N:21]([CH2:23][CH2:24][OH:25])[N:22]=3)[CH2:17][C@@:11]1([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@H:12]([O:26][CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=1)[CH2:13][CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[H-].[Na+]>>[CH2:3]([N:10]1[C@@H:15]2[C@H:16]([C:18]3[N:19]=[N:20][N:21]([CH2:23][CH2:24][O:25][CH3:2])[N:22]=3)[CH2:17][C@@:11]1([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@H:12]([O:26][CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[C:30]([C:38]([F:40])([F:41])[F:39])[CH:29]=1)[CH2:13][CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

4

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86586764HCID 86586764, compound2×

Product 1

HCID 86586763HCID 86586763, compoundYield 95%

Conditions

Temperature
50 °C

Procedure

Iodomethane, 85 mg, 0.6 mmol was added to suspension of (1R*,2R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-[2-(2-hydroxyethyl)-2H-tetrazol-5-yl]-1-phenyl-8-azabicyclo[3.2.1]octane (Compound 3a in Table 3; 250 mg, 0.4 mmol) and sodium hydride (24 mg, 0.6 mmol, 60% in oil). The reaction mixture was stirred at 50° C. for 2 hours then quenched by addition of saturated ammonium chloride. The mixture was partitioned between ethyl acetate and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 1:2 ethyl acetate/iso-hexanes to yield the title compound (246 mg, 95%).

Workup

  1. customthen quenched by addition of saturated ammonium chloride
  2. customThe mixture was partitioned between ethyl acetate and brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel eluting with 1:2 ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-37af503cb46d40d790af886438ff6fee
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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