Triethylamine → (1R*,2R*,5S*,6R*)-8-Benzyl-2-[3,5-bis(trifluoromethyl)benzoyloxy]-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088116Notes

Reaction equation

HRID 2088116 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:6](Cl)=[O:7].[CH2:18]([N:25]1[C@@H:30]2[C@H:31]([C:33]#[N:34])[CH2:32][C@@:26]1([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C@H:27]([OH:35])[CH2:28][CH2:29]2)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(CC)CC)C>ClCCl>[CH2:18]([N:25]1[C@@H:30]2[C@H:31]([C:33]#[N:34])[CH2:32][C@@:26]1([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C@H:27]([O:35][C:6](=[O:7])[C:5]1[CH:9]=[C:10]([C:12]([F:13])([F:14])[F:15])[CH:11]=[C:3]([C:2]([F:1])([F:16])[F:17])[CH:4]=1)[CH2:28][CH2:29]2)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 69890225(1R*,2R*,5S*,6R*)-8-Benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol

Product 1

HCID 86586649(1R*,2R*,5S*,6R*)-8-Benzyl-2-[3,5-bis(trifluoromethyl)benzoyloxy]-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octaneYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3,5-Bis(trifluoromethyl)benzoyl chloride (2.76 g, 10 mmol) was added dropwise to an ice-cold solution of (1R*,2R*,5S*,6R*)-8-benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 31; 3 g, 9.4 mmol), triethylamine (2 g, 20 mmol) and 4-N,N-dimethylaminopyridine (200 mg, 1.6 mmol) in dichloromethane (30 ml). The mixture was stirred at room temperature for 20 hours. The mixture was concentrated in vacuo then partitioned between ethyl acetate and brine. The organics were separated, dried (MgSO4), filtered and concentrated. The residue was chromatographed on silica gel eluting with 10 and 20% ethyl acetate/iso-hexanes to afford the title compound (4.87 g, 93%).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthen partitioned between ethyl acetate and brine
  3. customThe organics were separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel eluting with 10 and 20% ethyl acetate/iso-hexanes

Sources & evidence

ORD record
ord-9ac820934b344996aafac7777a85e014
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

Loading…