Methyl iodide → 1-tert-Butyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate

HRID 990097Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:11]([O:15][C:16]([N:18]1[CH2:28][CH2:27][CH2:26][CH:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].I[CH3:30]>O1CCCC1>[C:11]([O:15][C:16]([N:18]1[CH2:28][CH2:27][CH2:26][C:20]([CH3:30])([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19]1)=[O:17])([CH3:12])([CH3:13])[CH3:14]

Participants

Conditions

Temperature: -78 °C

Procedure

Potassium bis(trimethylsilyl)amide (1200 ml, 0.5M in toluene, 0.6 mol) was added to a 3-necked 3-l flask equipped with an overhead stirrer, followed by tetrahydrofuran (90 ml) and the solution was cooled to −78° C. Ethyl N-(t-butyloxycarbonyl)nipecotate (100 g, 0.39 mol) in tetrahydrofuran (90 ml) was added dropwise and the resulting solution allowed to age for 15 minutes. Iodomethane (37.4 ml, 85.2 g, 0.6 mol) was added dropwise to the stirred solution keeping the temperature below −70° C. The resulting mixture was stirred at room temperature overnight and was evaporated under reduced pressure. The residue was partitioned between ethyl acetate and water and the organic layer was washed with brine, dried (sodium sulphate) and evaporated to give a yellow oil. This was purified on a plug of silica using dichloromethane as eluant to afford the product (94 g, 90%) as a pale yellow oil.

Workup

customequipped with an overhead stirrer
customthe temperature below −70° C
customwas evaporated under reduced pressure
customThe residue was partitioned between ethyl acetate and water
washthe organic layer was washed with brine
dry with materialdried (sodium sulphate)
customevaporated
customto give a yellow oil
customThis was purified on a plug of silica

Sources & evidence

ORD record: ord-fd029e7ae3814af1b8eb4f75ee4b2fb5
Source dataset: uspto-grants-2002_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06458830B1

Reaction notes

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