Hydrochloric Acid → 1'-Benzyl-5-chloro-3H-spiro[isobenzofuran-1,4'-piperidine]

HRID 270092Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([C:17]3[CH:18]=[CH:19][C:20]([Cl:22])=[CH:21][C:16]=3[C:15](=O)[O:14]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[OH-].[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([C:17]3[CH:18]=[CH:19][C:20]([Cl:22])=[CH:21][C:16]=3[CH2:15][O:14]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 1′-benzyl-5-chloro-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one (1.1 g, 3.35 mmol) in THF (12 mL) was added 1 M solution of borane complex in THF (7 mL, 7.0 mmol) slowly at 0° C. After addition was complete reaction mixture was kept at room temperature for 30 min, then kept at reflux overnight, cooled to 0° C. and 6M aqueous HCl (3.5 mL) was added slowly. The reaction mixture was kept at reflux for 5 h, cooled to 0° C., pH of the reaction mixture was adjusted to 10 by addition of aqueous NaOH (6M) and the whole was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulphate (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by silica gel flash chromatography (0-30% ethyl acetate in petroleum ether) to give the subtitled compound (1.0 g).

Workup

additionAfter addition
temperatureat reflux overnight
temperatureat reflux for 5 h
temperaturecooled to 0° C.
extractionthe whole was extracted with ethyl acetate
washThe organic layer was washed with water
dry with materialdried over sodium sulphate (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel flash chromatography (0-30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-4fa3fb46812240c59a78ebdd85624430
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449475B2

Reaction notes

Loading…