HCID 86586761, compound → HCID 86586762, compound

HRID 2088212Notes

Reaction equation

HRID 2088212 reaction equation
[CH3:1][Mg]Br.[CH2:4]([N:11]1[C@@H:16]2[C@H:17]([C:19]3[N:20]=[N:21][N:22]([CH2:24][C:25](=[O:27])[CH3:26])[N:23]=3)[CH2:18][C@@:12]1([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C@H:13]([O:28][CH2:29][C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[C:32]([C:40]([F:43])([F:42])[F:41])[CH:31]=1)[CH2:14][CH2:15]2)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>C1COCC1>[CH2:4]([N:11]1[C@@H:16]2[C@H:17]([C:19]3[N:20]=[N:21][N:22]([CH2:24][C:25]([OH:27])([CH3:1])[CH3:26])[N:23]=3)[CH2:18][C@@:12]1([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C@H:13]([O:28][CH2:29][C:30]1[CH:35]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:33]=[C:32]([C:40]([F:42])([F:43])[F:41])[CH:31]=1)[CH2:14][CH2:15]2)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 86586761HCID 86586761, compound2×HCID 178418573HCID 178418573, compound

Product 1

HCID 86586762HCID 86586762, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methylmagnesium bromide (3.0M solution in THF, 0.7 ml, 2.1 mmol) was added dropwise to a −78° C. solution of (1R*12R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-[2-(2-oxopropyl)-2H-tetrazol-5-yl]-1-phenyl-8-azabicyclo[3.2.1]octane (Compound 3i in Table 3; 1.1 g, 1.7 mmol) in THF (25 ml). The mixture was warmed to 0° C. for 30 minutes then quenched by addition of saturated ammonium chloride. The mixture was partitioned between ethyl acetate and brine. The organic layer was separated, dried (MgSO4), filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 2.5, 5 and 10% ethyl acetate/iso-hexanes to yield the title compound (0.43 g, 39%).

Workup

  1. customthen quenched by addition of saturated ammonium chloride
  2. customThe mixture was partitioned between ethyl acetate and brine
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed on silica gel eluting with 2.5, 5 and 10% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-49b6fc5bc9a34aa4a3d325bf2fe891b7
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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