Methyl iodide → 1-Tert-butyl-4-chloropiperidine

HRID 59710

Reaction equation

HRID 59710 reaction equation
CI.C[C:4]1[C:13]2[C:8](=CC=CC=2)[CH2:7][CH2:6][N:5]=1.C[Mg][Cl:16].[CH3:17][C:18]1([CH3:29])[C:27]2C(=CC=CC=2)CCN1C>>[C:18]([N:5]1[CH2:4][CH2:13][CH:8]([Cl:16])[CH2:7][CH2:6]1)([CH3:29])([CH3:27])[CH3:17]

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 2315021-Methyl-3,4-dihydroisoquinolineHCID 18382671HCID 18382671, compoundHCID 178418332HCID 178418332, compound2×

Product 1

HCID 114238721-Tert-butyl-4-chloropiperidine

Procedure

The imine bond can be activated by quaternization to allow the nucleophilic addition of Grignard reagent. Methyl iodide was added to 1-methyl-3,4-dihydroisoquinoline, generating the iminium salt 1,2-dimethyl-3,4-dihydroisoquinolinium iodide.20 This iminium salt is more reactive than the imine. Methylmagnesium chloride reacted with the iminium, generating 1,1,2-trimethyl-1,2,3,4-tetrahydroisoquinoline. The reaction of methylmagnesium chloride with the iminium salt N-isopropylidene-4-chloropiperidinium chloride gave 1-tert-butyl-4-chloropiperidine.21

Sources & evidence

ORD record
ord-651143b2b3ac4b9082fb05b5c5ffe788
Source dataset
uspto-grants-2016_09
Patent number
US09440948B2

Linked notes

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