Chloroiodomethane → Tert-butyl 4-[(cyclopropyloxy)methyl]piperidine-1-carboxylate

HRID 69125Notes

Reaction equation

[CH2:1]([Zn]CC)C.[CH:6]([O:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)=[CH2:7].ClCI.[Cl-].[NH4+]>ClCCCl>[CH:6]1([O:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH2:1][CH2:7]1

Participants

Conditions

Temperature: -40 °C

Procedure

Under a nitrogen atmosphere, 63 mL of diethylzinc (1.0 M hexane solution) was added to 92 mL of 1,2-dichloroethane at −40° C., and subsequently a solution of 2.5 g of tert-butyl 4-[(vinyloxy)methyl]piperidine-1-carboxylate in 134 mL of 1,2-dichloroethane was added thereto, followed by stirring at −40° C. for 30 minutes. 7.5 mL of chloroiodomethane was added thereto, followed by stirring for 4 hours while elevating the temperature from −40° C. to −15° C. To the reaction mixture was added portionwise a saturated aqueous ammonium chloride solution, followed by extraction with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to obtain 2.0 g of tert-butyl 4-[(cyclopropyloxy)methyl]piperidine-1-carboxylate.

Workup

stirringby stirring for 4 hours
customfrom −40° C. to −15° C
extractionfollowed by extraction with chloroform
washThe organic layer was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record: ord-9821b56f27b44c2a8fa99bc09a358bbf
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822448B2

Reaction notes

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