Triethylamine hydrochloride → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-1-phenyl-6-(tetrazol-5-yl)-8-azabicyclo[3.2.1]octane

HRID 2088219Notes

Reaction equation

HRID 2088219 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]#[N:17])[CH2:15][C@@:9]1([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C@H:10]([O:18][C@H:19]([C:29]1[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[C:31]([C:39]([F:42])([F:41])[F:40])[CH:30]=1)[CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:49]=[N+:50]=[N-:51].[Na+].[Cl-].[NH4+].Cl.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[NH:51][N:50]=[N:49][N:17]=3)[CH2:15][C@@:9]1([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C@H:10]([O:18][C@H:19]([C:29]1[CH:34]=[C:33]([C:35]([F:37])([F:38])[F:36])[CH:32]=[C:31]([C:39]([F:40])([F:41])[F:42])[CH:30]=1)[CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11130Triethylamine hydrochlorideHCID 25517Ammonium ChlorideHCID 33557Sodium Azide2×HCID 86586768(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 178506189(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-1-phenyl-6-(tetrazol-5-yl)-8-azabicyclo[3.2.1]octaneYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-2-phenylmethoxyethoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane (Example 157; 0.7105 g, 1.07 mmol), sodium azide (0.2087 g, 3.21 mmol) and ammonium chloride (0.172 g, 3.21 mmol) in dimethylformamide (10 ml) were heated at 120° C. for 18 hours. A further 3.0 eq of sodium azide and 3.0 eq of triethylamine hydrochloride were added and the mixture heated for a further 18 hours. The mixture was diluted with ethyl acetate and washed with water. The organics were collected, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography, eluting with 5% methanol/dichloromethane to give the title compound (400 mg, 53%).

Workup

  1. temperaturethe mixture heated for a further 18 hours
  2. washwashed with water
  3. customThe organics were collected
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography
  7. washeluting with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-624d0a7cfd25463eaf8f27a916c50649
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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