Sulfuric Acid → 4-(3-(4-(Azido(cyclopentyl)(phenyl)methyl)piperidin-1-yl)propoxy)benzonitrile

HRID 1503346Notes

Reaction equation

HRID 1503346 reaction equation
[CH:1]1([C:6](O)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][O:16][C:17]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=3)[CH2:9][CH2:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N-:32]=[N+:33]=[N-:34].[Na+].OS(O)(=O)=O.[NH4+].[OH-]>C(Cl)(Cl)Cl>[N:32]([C:6]([CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[CH2:9][CH2:8]1)=[N+:33]=[N-:34]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 14923Ammonium HydroxideHCID 33557Sodium AzideHCID 469266324-(3-(4-(Cyclopentyl(hydroxy)(phenyl)methyl)piperidin-1-yl)propoxy)benzonitrile

Product 1

HCID 1177376164-(3-(4-(Azido(cyclopentyl)(phenyl)methyl)piperidin-1-yl)propoxy)benzonitrileYield 10%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A CHCl3 (4.78 mL, 0.25 M) solution of 4-(3-(4-(cyclopentyl(hydroxy)(phenyl)methyl)piperidin-1-yl)propoxy)benzonitrile (0.5 g, 1.19 mmol) and sodium azide (1.16 g, 17.9 mmol) was cooled to 0° C. To the solution H2SO4 was added dropwise (0.28 mL, 9.3 mmol). The mixture was allowed to warm to rt over 4 h with stirring, then re-cooled to 0° C. and treated with NH4OH till pH was basic. The biphasic solution was extracted with DCM (3×) and the organic layers combined and dried over MgSO4. Concentration under reduced pressure and drying in vacuo afforded a crude oil. Purification by flash chromatography (DCM, MeOH, NH4OH) afforded 4-(3-(4-(azido(cyclopentyl)(phenyl)methyl)piperidin-1-yl)propoxy)benzonitrile (45 mg, 10%): LC-MS (>98%) m/z=444.3 [M+H].

Workup

  1. temperaturere-cooled to 0° C.
  2. extractionThe biphasic solution was extracted with DCM (3×)
  3. dry with materialdried over MgSO4
  4. concentrationConcentration under reduced pressure
  5. customdrying in vacuo
  6. customafforded a crude oil
  7. customPurification by flash chromatography (DCM, MeOH, NH4OH)

Sources & evidence

ORD record
ord-de5556380fbe493fbaaf262b6c994185
Source dataset
uspto-grants-2015_12
Patent number
US09212180B2

Reaction notes

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