Hydrochloric Acid → HCID 23004130, compound

HRID 964217Notes

Reaction equation

HRID 964217 reaction equation
[C:1]1([C:7]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]#[N:16])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:24]COCC.F[B-](F)(F)F.C[O+](C)C.[BH4-].[Na+]>C(Cl)Cl.CO>[CH3:24][NH:16][CH2:15][CH2:14][CH2:13][N:10]1[CH2:9][CH2:8][C:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:12][CH2:11]1

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 4311764Sodium borohydrideHCID 155128643-(4,4-Diphenylpiperidin-1-yl)propionitrile

Product 1

HCID 23004130HCID 23004130, compoundYield 41.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-(4,4-diphenylpiperidin-1-yl)propionitrile (5.00 g, 17.2 mmol, 1.00 equiv) in CH2Cl2 (40 mL) was added HCl in ether (1.0M, 22.4 mL, 22 mmol, 1.3 equiv). After removal of the solvents, the residue and trimethyloxonium tetrafluoroborate (9.67 g, 65.4 mmol, 3.80 equiv) were stirred in refluxing anhydrous CH2Cl2 (80 mL) under argon for 44 hours. The mixture was cooled to 0° C., anhydrous MeOH (5 mL) was added, and stirring was continued for 1 hour at 0° C. The solvents were removed and the residue was dissolved in anhydrous MeOH (30 mL). Sodium borohydride (5.20 g, 138 mmol, 8.00 equiv) was added at 0° C., and stirring was continued at this temperature under argon for 2 hours. The solution was acidified to pH 1 by slow addition of 6N aqueous HCl (40 mL) at 0° C. and stirred for 3 hours at room temperature. After removal of the solvents, water (30 mL) was added and the mixture was basified to pH 9 by addition of 6N aqueous NaOH. The mixture was extracted with CH2Cl2 (3×100 mL), and the combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, EtOAc-MeOH-isopropylamine 9:1:0 to 5:1:0.2) to give 2.18 g (41%) of yellow solid, which was characterized spectroscopically.

Workup

  1. customAfter removal of the solvents
  2. customThe solvents were removed
  3. dissolutionthe residue was dissolved in anhydrous MeOH (30 mL)
  4. stirringstirring
  5. waitwas continued at this temperature under argon for 2 hours
  6. stirringstirred for 3 hours at room temperature
  7. customAfter removal of the solvents, water (30 mL)
  8. additionwas added
  9. additionthe mixture was basified to pH 9 by addition of 6N aqueous NaOH
  10. extractionThe mixture was extracted with CH2Cl2 (3×100 mL)
  11. dry with materialthe combined organic solutions were dried over MgSO4
  12. concentrationconcentrated
  13. customThe residue was purified by flash chromatography (SiO2, EtOAc-MeOH-isopropylamine 9:1:0 to 5:1:0.2)

Sources & evidence

ORD record
ord-caa4e39ec4bf48849aff1f33bdd4ba23
Source dataset
uspto-grants-1998_06
Patent number
US05767131

Reaction notes

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