Hydrochloric Acid → 8-Benzyl-8-azabicyclo(3.2.1)octan-3-amine

HRID 2079456Notes

Reaction equation

[CH2:1]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11](=[N:16]O)[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na].Cl>C(O)CCCC>[CH2:1]([N:8]1[CH:9]2[CH2:15][CH2:14][CH:13]1[CH2:12][CH:11]([NH2:16])[CH2:10]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 5 °C

Procedure

To a solution of oxime 99 (7.65 g, 33 mmol) in 1-pentanol (130 mL) at 120° C., was added sodium metal (7.6 g, 0.33 mol, 10.0 equiv) portionwise over 2 h. The mixture was stirred and heated under reflux conditions for 5 h, then was cooled to 5° C. The reaction mixture was slowly acidified with 6M HCl to a pH of 2 then was further extracted with 6M HCl (3×100 mL). The aqueous layer was gradually made basic by the addition of 5M NaOH to a pH of 10. The resulting aqueous solution was extracted with EtOAc (3×100 mL) and the combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. Purification of the crude material via column chromatography (5-10% MeOH/CH2Cl2) afforded pure 8-benzyl-8-azabicyclo[3.2.1]octan-3-amine 100 as a solid (2.60 g, 36%).

Workup

temperatureheated under reflux conditions for 5 h
extractionthen was further extracted with 6M HCl (3×100 mL)
additionThe aqueous layer was gradually made basic by the addition of 5M NaOH to a pH of 10
extractionThe resulting aqueous solution was extracted with EtOAc (3×100 mL)
dry with materialthe combined organic extracts were dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the crude material via column chromatography (5-10% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-9d6025a206324e448f0ce55e23b30f9d
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932235B2

Reaction notes

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