Water → (1R*,2R*,5R*)-8-Benzyl-2-(3,5-bis(trifluoromethyl)benzoyl)-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane

HRID 2088102Notes

Reaction equation

HRID 2088102 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[CH2:14][CH2:15][C@@:9]1([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[C@H:10](O)[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:31][C:32]([F:47])([F:46])[C:33]1[CH:34]=[C:35]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[C:36](Cl)=[O:37].O>ClCCl.CN(C)C1C=CN=CC=1>[CH2:1]([N:8]1[C@H:13]2[CH2:14][CH2:15][C@:9]1([C:17]1[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=1)[C@H:10]([C:36](=[O:37])[C:35]1[CH:34]=[C:33]([C:32]([F:47])([F:46])[F:31])[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=1)[CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 69889560(1R*,2R*,5R*)-8-Benzyl-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octan-2-ol

Product 1

HCID 86586644(1R*,2R*,5R*)-8-Benzyl-2-(3,5-bis(trifluoromethyl)benzoyl)-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octaneYield 58%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(1R*,2 R*,5R*)-8-Benzyl-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octan-2-ol (Description 15; 1.23 g, 3.95 mmol), and triethylamine (0.61 ml, 4.35 mmol) in dichloromethane were stirred with 4-dimethylaminopyridine (5 crystals) and 3,5-bis(trifluoromethyl)benzoyl chloride at room temperature for a weekend. The reaction mixture was poured into water and extracted with dichloromethane (×3), dried (MgSO4) and concentrated in vacuo to give a yellow oil. This was purified by flash column chromatography [10%-20% ethyl acetate in iso-hexane] to give the title compound as a yellow solid (1.27 g, 58%).

Workup

  1. extractionextracted with dichloromethane (×3)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give a yellow oil
  5. customThis was purified by flash column chromatography [10%-20% ethyl acetate in iso-hexane]

Sources & evidence

ORD record
ord-580dfbbf6deb4487a384d112ea18aadd
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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