Toluene → Tert-butyl-5-(2-tetrahydropyran-2-yloxyethoxy)-2-azabicyclo[2.2.1]heptane-2-carboxylate

HRID 928564Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[CH2:10][CH:11]2[OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].C1(C)C=CC=CC=1.Br[CH2:26][CH2:27][O:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][O:30]1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[CH2:10][CH:11]2[O:15][CH2:26][CH2:27][O:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][O:30]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 60 °C

Procedure

Tert-butyl-5-hydroxy-2-azabicyclo[2.2.1]heptane-2-carboxylate (1.5 g, 7.0 mmol) and tetrabutylammonium bromide (0.35 g, 0.70 mmol) were stirred in sodium hydroxide (10 M) (30 mL, 1600 mmol)/toluene (30 mL) and heated to 60° C. 2-(2-Bromoethoxy)tetrahydropyran (4.4 g, 21 mmol) was added in 4 portions over 2 hours and heating continued overnight. Further 2-(2-bromoethoxy)tetrahydropyran (1 eq) was added and the reaction heated for a further 3 hours. The reaction mixture was diluted with DCM, washed with water, dried over Na2SO4 and concentrated in vacuo to afford a yellow oil. The reaction mixture was purified by flash chromatography, eluting with DCM then 90/10 DCM/MeOH to afford tert-butyl-5-(2-tetrahydropyran-2-yloxyethoxy)-2-azabicyclo[2.2.1]heptane-2-carboxylate (1.08 g).

Workup

temperatureheating
temperaturethe reaction heated for a further 3 hours
washwashed with water
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customto afford a yellow oil
customThe reaction mixture was purified by flash chromatography
washeluting with DCM

Sources & evidence

ORD record: ord-dc1b5526a4a74194bed32b4e5bf719b2
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290511B2

Reaction notes

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