1,4-Dioxane hydrochloride → HCID 178462017, compound

HRID 1691768Notes

Reaction equation

HRID 1691768 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:12][N:11]=[N:10][N:9]=2)[CH:5]=[C:4]([F:13])[C:3]=1[N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][N:21]([C@@H:29]([C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:34]=[CH:33][CH:32]=2)[CH3:30])C(=O)OC(C)(C)C)[CH:16]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:15]1.Cl.O1CCOCC1>>[F:13][C:4]1[CH:5]=[C:6]([C:8]2[NH:12][N:11]=[N:10][N:9]=2)[CH:7]=[C:2]([F:1])[C:3]=1[N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][NH:21][C@@H:29]([C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:34]=[CH:33][CH:32]=2)[CH3:30])[CH:16]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH2:15]1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 178461650HCID 178461650, compound

Product 1

HCID 178462017HCID 178462017, compoundYield 91.8%

Procedure

To 205 mg of tert-butyl ({1-[2,6-difluoro-4-(1H-tetrazole-5-yl)phenyl]-3-phenylpiperidin-4-yl}methyl)[(1R)-1-(1-naphthyl)ethyl]carbamate was added 2.0 mL of a 4 M hydrogen chloride/1,4-dioxane solution, followed by stirring at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and to the residue was then added a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol) to obtain 158 mg of (1R)—N-({1-[2,6-difluoro-4-(1H-tetrazol-5-yl)phenyl]-3-phenylpiperidin-4-yl}methyl)-1-(1-naphthyl)ethaneamine. 2.0 mL of hydrogen chloride/1,4-dioxane solution was added thereto, followed by concentration under reduced pressure, and to the obtained residue was then added about 3 mL of isopropanol, followed by heating. The mixture was left to be cooled to room temperature, and the precipitate was collected by filtration, and dried under reduced pressure to obtain 153 mg of (1R)—N-({1-[2,6-difluoro-4-(1H-tetrazol-5-yl)phenyl]-3-phenylpiperidin-4-yl}methyl)-1-(1-naphthyl)ethaneamine hydrochloride as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionto the residue was then added a saturated aqueous sodium hydrogen carbonate solution
  3. extractionfollowed by extraction with chloroform
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-57b854d694b54dee9f569e99a4eacd3b
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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