1-Chloroethyl chloroformate → 3,4-Dihydro-2H-spiro[naphthalene-1,4'-piperidine]--hydrogen chloride (1/1)

HRID 1674719Notes

Reaction equation

C[N:2]1[CH2:7][CH2:6][C:5]2([C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:10][CH2:9][CH2:8]2)[CH2:4][CH2:3]1.[Cl:17]C(OC(Cl)C)=O>ClCCCl>[ClH:17].[NH:2]1[CH2:7][CH2:6][C:5]2([C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:10][CH2:9][CH2:8]2)[CH2:4][CH2:3]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of the N-methylpiperidine (A1) (37 g, 172 mmol) in 1,2-dichloroethane (250 ml) was added 1-chloroethyl chloroformate (20.7 ml, 190 mmol) at 0° C. The solution turned to a solid. After 0.5 hours at room temperature, the reaction mixture was heated under reflux for 15 hours. After concentration, the residue was dissolved in methanol (250 ml) and heated at 50° C. for 2 hours. The mixture was cooled to room temperature, the precipitate was filtered and washed with ether to produce 3,4-dihydro-2H-spiro[naphthalene-1,4′-piperidine] HCl salt (A2). The filtrate was concentrated, suspended in ether, filtered, and the solid washed with MeOH and ether to give additional 3,4-dihydro-2H-spiro[naphthalene -1,4′-piperidine] HCl salt (A2). LC-MS: m/e=202.1 (M+H). Rt=1.61 min. 1H-NMR (500 MHz, CDCl3): 9.74 (s, 2H), 7.58 (d, J=7.9, 1H), 7.22 (t, J=7.8, 1H), 7.14 (t, J=7.9, 1H), 7.08 (d, J=8.0, 1H), 3.47 (d, J=12.4, 2H), 3.22-3.18 (m, 2H), 2.88 (t, J=4.9, 2H), 2.81 (t, J=6.2, H), 2.60 (td, 2H), 1.93-1.89 (m, 2H), 1.83-1.77 (m, 2H).

Workup

temperaturethe reaction mixture was heated
temperatureunder reflux for 15 hours
concentrationAfter concentration
dissolutionthe residue was dissolved in methanol (250 ml)
temperatureThe mixture was cooled to room temperature
filtrationthe precipitate was filtered
washwashed with ether

Sources & evidence

ORD record: ord-709b926362a34799966fbffe002bb778
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003660B2

Reaction notes

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