Potassium Carbonate → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-(1-methoxycarbonylmethyl-1H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088208Notes

Reaction equation

HRID 2088208 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[NH:20][N:19]=[N:18][N:17]=3)[CH2:15][C@@:9]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:10]([O:21][CH2:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:44][C:45]([O:47][CH3:48])=[O:46].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[N:17]([CH2:44][C:45]([O:47][CH3:48])=[O:46])[N:18]=[N:19][N:20]=3)[CH2:15][C@@:9]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:10]([O:21][CH2:22][C:23]1[CH:24]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 178506223HCID 178506223, compound

Product 1

HCID 86586756(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-(1-methoxycarbonylmethyl-1H-tetrazol-5-yl)-1-phenyl-8-azabicyclo[3.2.1]octane

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-6-(tetrazol-5-yl)-8-azabicyclo[3.2.1]octane (Example 138; 2 g, 3.4 mmol), methyl bromoacetate (0.5 ml, 5.1 mmol) and potassium carbonate (0.75 g, 0.51 mmol) were stirred in acetonitrile (20 ml) at 45° C. for 90 minutes. After this time the mixture was concentrated in vacuo and the residue partitioned between brine and ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated. The residual clear oil was chromatographed on silica gel eluting with 10, 20 and 50% ethyl acetate/iso-hexanes to yield the title compounds: isomer A (1.2 g, 54%) and isomer B (0.9 g, 40%).

Workup

  1. concentrationAfter this time the mixture was concentrated in vacuo
  2. customthe residue partitioned between brine and ethyl acetate
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residual clear oil was chromatographed on silica gel eluting with 10, 20 and 50% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-72315bd0ab5449be8ed39fc5c893ca9e
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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