1,4-Dioxane hydrochloride → 4-({[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]carbonyl}oxy)benzoic acid

HRID 1691698Notes

Reaction equation

HRID 1691698 reaction equation
C(OC([N:8]([CH2:21][CH:22]1[CH:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[F:34])[CH2:26][CH2:25][N:24]([C:35]([O:37][C:38]2[CH:46]=[CH:45][C:41]([C:42]([OH:44])=[O:43])=[CH:40][CH:39]=2)=[O:36])[CH2:23]1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=O)(C)(C)C.Cl.O1CCOCC1>>[F:34][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[CH:27]1[CH2:26][CH2:25][N:24]([C:35]([O:37][C:38]2[CH:46]=[CH:45][C:41]([C:42]([OH:44])=[O:43])=[CH:40][CH:39]=2)=[O:36])[CH2:23][CH:22]1[CH2:21][NH:8][C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10]

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 669061994-({[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(2-fluorophenyl)piperidin-1-yl]carbonyl}oxy)benzoic acid

Product 1

HCID 591786564-({[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]carbonyl}oxy)benzoic acidYield 75.4%

Procedure

To 213 mg of 4-({[3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(2-fluorophenyl)piperidin-1-yl]carbonyl}oxy)benzoic acid was added 3.0 mL of a 4 M hydrogen chloride/1,4-dioxane solution, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and to the obtained residue was added chloroform, followed by washing with a saturated aqueous sodium hydrogen carbonate solution (1.0 mL). The organic layer was dried over anhydrous sodium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate, and hexane was added thereto. Then, the precipitate was isolated by filtration. It was dried under reduced pressure to obtain 135 mg of 4-({[4-(2-fluorophenyl)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)piperidin-1-yl]carbonyl}oxy)benzoic acid as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionto the obtained residue was added chloroform
  3. washby washing with a saturated aqueous sodium hydrogen carbonate solution (1.0 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. dissolutionThe obtained residue was dissolved in ethyl acetate
  8. additionhexane was added
  9. customThen, the precipitate was isolated by filtration
  10. customIt was dried under reduced pressure

Sources & evidence

ORD record
ord-7a3a2719bd6142f78df04fa9ee850250
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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