Sodium Hydroxide → 2-Oxobicyclo(3.1.0)hexane-6-carboxylic acid

HRID 1418248Notes

Reaction equation

HRID 1418248 reaction equation
C([C:3]12[CH:8]([C:9]([OH:11])=[O:10])[CH:7]1[CH2:6][CH2:5][C:4]2=[O:12])C.[OH-].[Na+]>>[O:12]=[C:4]1[CH2:5][CH2:6][CH:7]2[CH:3]1[CH:8]2[C:9]([OH:11])=[O:10]

Participants

3

Reactant 2

HCID 14798Sodium HydroxideHCID 54094213HCID 54094213, compound

Product 1

HCID 102194732-Oxobicyclo(3.1.0)hexane-6-carboxylic acid

Procedure

(+)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid may be prepared by reacting carbethoxymethyl dimethylsulfonium bromide with 2-cyclopenten-1-one in the presence of a base, such as 1,8-diazabicyclo[5.4.0]undec-7-ene to afford ethyl 2-oxobicyclo[3.1.0]hexane-6-carboxylate. This ester may then be reacted with an aqueous solution of potassium cyanide or sodium cyanide and ammonium carbonate to produce an intermediate hydantoin, (the Bucherer-Bergs reaction), which is then hydrolysed using sodium hydroxide, to afford a diastereomeric mixture of diethyl 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. The desired diastereomer may be obtained by crystallization with oxalic acid. This diastereomer may then be resolved by forming a crystalline salt with (+)-di-p-toluoyl-D-tartaric acid and recovering (-)-diethyl 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate. Hydrolysis of this diester using aqueous sodium hydroxide gives (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid. Alternatively, the ethyl 2-oxobicyclo[3.1.0]hexane-6-carboxylic acid may be hydrolysed using sodium hydroxide to give 2-oxobicyclo[3.1.0]hexane-6-carboxylic acid. This acid may then be resolved by forming a crystalline salt with (S)-1-phenylethylamine and recovering (+)-2-oxobicyclo[3.1.0]hexane-6-carboxylic acid. This acid may then be converted into (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid by reaction with an aqueous solution of potassium cyanide or sodium cyanide and ammonium carbonate to produce an intermediate hydantoin (the Bucherer-Bergs reaction) followed by hydrolysis of the hydantoin using sodium hydroxide. This procedure may also be modified by performing the resolution step on the hydantoin rather than on the 2-oxobicyclo[3.1.0]hexane-6-carboxylic acid. In this case, (R)-1-phenylethylamine has been found to be a suitable resolving agent.

Sources & evidence

ORD record
ord-f218e48106264b8787b24aa73ab18e8e
Source dataset
uspto-grants-1999_03
Patent number
US05882671

Reaction notes

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