Water → HCID 178506223, compound

HRID 2088202Notes

Reaction equation

HRID 2088202 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]#[N:17])[CH2:15][C@@:9]1([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@H:10]([O:18][CH2:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[CH:21]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:40]=[N+:41]=[N-:42].[Na+].[Cl-].[NH4+].O>CN(C)C=O>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[NH:42][N:41]=[N:40][N:17]=3)[CH2:15][C@@:9]1([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@H:10]([O:18][CH2:19][C:20]1[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[C:22]([C:30]([F:31])([F:32])[F:33])[CH:21]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 86586749(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 178506223HCID 178506223, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane (Example 137; 4 g, 7.4 mmol), sodium azide (1.4 g, 22 mmol) and ammonium chloride (1.2 g, 22 mmol) were stirred at 120° C. in N,N-dimethylformamide (15 ml) for 20 hours. On cooling to room temperature the mixture was poured into water (250 ml) and extracted (×2) with ethyl acetate. The combined organic extracts were washed (×3) with water then dried (MgSO4), filtered and concentrated. Residue was chromatographed on silica gel eluting with 1, 2 and 4% methanol/dichloromethane to give the title compound (2.7 g, 63%).

Workup

  1. extractionextracted (×2) with ethyl acetate
  2. washThe combined organic extracts were washed (×3) with water
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customResidue was chromatographed on silica gel eluting with 1, 2 and 4% methanol/dichloromethane

Sources & evidence

ORD record
ord-fa86a95a4bb54456a34a1fd057b5c7d1
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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