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

HRID 1096169Notes

Reaction equation

HRID 1096169 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

5

Reactant 3

HCID 11644ChloroiodomethaneHCID 10584700tert-Butyl 3-hydroxy-4-methylidenepiperidine-1-carboxylateHCID 178418750HCID 178418750, compound

Product 1

HCID 44541812(4S)-6-Azaspiro[2.5]octan-4-ol hydrochlorideYield 36,664.699%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of diethylzinc (1.1 M solution in toluene, 37.5 ml, 0.04 mmol) in DCE (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 DCE (10 ml) was added, after which time the reaction was stirred for 0.5 h at 0° C. and then allowed to reach RT, stirring for a further 1 h. The reaction was then quenched by addition of sat. aq. ammonium chloride solution, separated, and the organic dried (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc/heptane 2:8→1:1) afforded the title product (2.4 g, 54%) as a crystalline solid. MS: 228.2 (MH+).

Workup

  1. additionwas added
  2. customto reach RT
  3. stirringstirring for a further 1 h
  4. customThe reaction was then quenched by addition of sat. aq. ammonium chloride solution
  5. customseparated
  6. dry with materialthe organic dried (Na2SO4)
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (EtOAc/heptane 2:8→1:1)

Sources & evidence

ORD record
ord-a0526033810b456a9d18ec2fcec36d06
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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