Hydrochloric Acid → 4-[3-(3,8-Diazabicyclo[3.2.1]oct-8-yl)-2-hydroxypropoxy]benzonitrile

HRID 1743704Notes

Reaction equation

HRID 1743704 reaction equation
C([N:8]1[CH2:14][CH:13]2[N:15]([CH2:16][CH:17]([OH:28])[CH2:18][O:19][C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=3)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)C1C=CC=CC=1.Cl>C(#N)C>[CH:13]12[N:15]([CH2:16][CH:17]([OH:28])[CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]([C:24]#[N:25])=[CH:26][CH:27]=3)[CH:10]([CH2:11][CH2:12]1)[CH2:9][NH:8][CH2:14]2

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 222354394-[3-(3-Benzyl-3,8-diazabicyclo[3.2.1]oct-8-yl)-2-hydroxypropoxy]benzonitrile

Product 1

HCID 222357074-[3-(3,8-Diazabicyclo[3.2.1]oct-8-yl)-2-hydroxypropoxy]benzonitrileYield 38%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a cold solution of 4-[3-(3-benzyl-3,8-diazabicyclo[3.2.1.]oct-8-yl)-2-hydroxypropoxy]benzonitrile (5.74 g, 15.2 mmol; from step (a) above) in acetonitrile (100 mL) there was added 12 M HCl (3.2 mL). The reaction mixture was stirred for 15 minutes, concentrated in vacuo and dried under high vacuum overnight. The resulting hydrochloride salt was added to a suspension of 10% Pd/C (700 mg) in methanol (500 mL). The reaction was then stirred under hydrogen (1 atmosphere of pressure) for 90 minutes. The mixture was filtered through Celite® and the filtrate concentrated in vacuo. The resulting residue was partitioned with saturated sodium bicarbonate (100 mL) and CH2Cl2 (150 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give the crude product. Flash chromatography on silica gel, eluting with CH2Cl2:CMA (4:1), gave 1.58 g (38%) of the sub-title compound.

Workup

  1. concentrationconcentrated in vacuo
  2. customdried under high vacuum overnight
  3. additionThe resulting hydrochloride salt was added to a suspension of 10% Pd/C (700 mg) in methanol (500 mL)
  4. stirringThe reaction was then stirred under hydrogen (1 atmosphere of pressure) for 90 minutes
  5. filtrationThe mixture was filtered through Celite®
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe resulting residue was partitioned with saturated sodium bicarbonate (100 mL) and CH2Cl2 (150 mL)
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give the crude product
  12. washFlash chromatography on silica gel, eluting with CH2Cl2

Sources & evidence

ORD record
ord-bc479355cbd24a1fbf2b37e79988f7d8
Source dataset
uspto-grants-2006_03
Patent number
US07012074B2

Reaction notes

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