Chloroiodomethane → (4S)-6-Azaspiro[2.5]octan-4-ol hydrochloride

HRID 559329Notes

Reaction equation

[CH2:1]([Zn]CC)C.[Cl:6]CI.C(OC([N:16]1[CH2:21][CH2:20][C:19](=[CH2:22])[CH:18]([OH:23])[CH2:17]1)=O)(C)(C)C>ClCCCl>[ClH:6].[CH2:22]1[C:19]2([CH2:20][CH2:21][NH:16][CH2:17][C@H:18]2[OH:23])[CH2:1]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of diethylzinc (1.1 M solution in toluene, 37.5 ml, 0.04 mmol) in 1,2-dichloroethane (80 ml) at 0° C. was added chloroiodomethane (5.99 ml, 0.08 mmol) under Ar. This mixture was stirred for 15 minutes before a solution of 3-hydroxy-4-methylene-piperidine-1-carboxylic acid tert-butyl ester (J. Org. Chem. 2001, 66, 2487) (4.19 g, 19.6 mmol) in 1,2-dichloroethane (10 ml) was added, after which time the reaction was stirred for 0.5 h at 0° C. and then allowed to reach room temperature, stirring for a further 1 h. The reaction was then quenched by addition of saturated aq. ammonium chloride solution, separated, and the organic dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 2:8-1:1) afforded the title product (2.4 g, 54%) as a crystalline solid MS: 228.2 (MH+).

Workup

additionwas added
customto reach room temperature
stirringstirring for a further 1 h
customThe reaction was then quenched by addition of saturated aq. ammonium chloride solution
customseparated
dry with materialthe organic dried (Na2SO4)
concentrationconcentrated
customPurification by flash column chromatography (ethyl acetate/heptane 2:8-1:1)

Sources & evidence

ORD record: ord-2e7967a7a7c94bc5bac14bfffe51af8e
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063042B2

Reaction notes

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