Mesoxalic acid → 8-Benzyl-8-azabicyclo(3.2.1)octan-3-one

HRID 2102878

Reaction equation

CO[CH:3]1[CH2:7][CH2:6][CH:5](OC)[O:4]1.Cl.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O=[C:20]([C:24](O)=O)[C:21](O)=O.C([O-])(=O)C.[Na+].[OH-].[Na+]>Cl>[CH2:11]([N:18]1[CH:6]2[CH2:5][CH2:24][CH:20]1[CH2:21][C:3](=[O:4])[CH2:7]2)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 2,5-dimethoxytetrahydrofuran (50 g, 378 mmol) in 0.025M aqueous hydrochloric acid (160 ml) was cooled to 0° C. and stirred for 16 hours. Benzylamine hydrochloride (65 g, 453 mmol), ketomalonic acid (55 g, 377 mmol) and an aqueous solution of sodium acetate (300 ml, 0.69M) were added and the reaction stirred at room temperature for 1 hour. The mixture was heated to 50° C. for a further 90 minutes then cooled in an ice bath and basified to pH12 with 2N aqueous sodium hydroxide solution. The layers were separated, and the aqueous phase extracted with ethyl acetate (3×). The combined organic solutions were washed with water, dried (MgSO4), filtered and evaporated under reduced pressure. The residual brown oil was distilled under reduced pressure (126° C./0.4 kPa) to afford the title compound as an off-white solid, 37.81 g.

Workup

stirringthe reaction stirred at room temperature for 1 hour
temperaturethen cooled in an ice bath
customThe layers were separated
extractionthe aqueous phase extracted with ethyl acetate (3×)
washThe combined organic solutions were washed with water
dry with materialdried (MgSO4)
filtrationfiltered
customevaporated under reduced pressure
distillationThe residual brown oil was distilled under reduced pressure (126° C./0.4 kPa)

Sources & evidence

ORD record: ord-839b530db7b544929b83f0f6e2767524
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576097B2

Linked notes

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