Dimethylformamide → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-[4-methyloxazol-2-yl]-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088168Notes

Reaction equation

HRID 2088168 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]([NH2:18])=[O:17])[CH2:15][C@@:9]1([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C@H:10]([O:19][CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:42][C:43](=O)[CH3:44].CN(C)C=O>C(OCC)C>[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([C:16]3[O:17][CH:42]=[C:43]([CH3:44])[N:18]=3)[CH2:15][C@@:9]1([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C@H:10]([O:19][CH2:20][C:21]1[CH:22]=[C:23]([C:31]([F:32])([F:33])[F:34])[CH:24]=[C:25]([C:27]([F:29])([F:30])[F:28])[CH:26]=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 6228DimethylformamideHCID 6571ChloroacetoneHCID 86586702(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxamide

Product 1

HCID 86586703(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-[4-methyloxazol-2-yl]-1-phenyl-8-azabicyclo[3.2.1]octaneYield 12%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (1R*,2R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl) phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxamide (Example 75; 250 mg, 0.44 mmol), chloroacetone (1 ml) and N,N-dimethylforamide (4 ml) was stirred at 120° C. for 24 hours. After cooling to room temperature the reaction mixture was diluted with diethyl ether (70 ml), washed with saturated aqueous NaHCO3, water and brine. The organic phase was dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate) to give the title compound (53 mg, 12%).

Workup

  1. temperatureAfter cooling to room temperature the reaction mixture
  2. washwashed with saturated aqueous NaHCO3, water and brine
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-a9dda9735dc5491b8bf400ae474ef76b
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

Loading…