1,2-Dibromoethane → Ethyl 1-acetylcyclopropane-1-carboxylate
Reaction equation
N[CH:2]1C2(CC2)CN[CH2:3]1.[C:9]([O:15][CH2:16][CH3:17])(=[O:14])[CH2:10][C:11]([CH3:13])=[O:12].BrCCBr>>[C:11]([C:10]1([C:9]([O:15][CH2:16][CH3:17])=[O:14])[CH2:3][CH2:2]1)(=[O:12])[CH3:13]Participants
Procedure
Taking 7-amino-5-azaspiro[2,4]heptane as an example, ethyl acetoacetate is first reacted with 1,2-dibromoethane in the presence of a base to give ethyl 1-acetyl-1-cyclopropanecarboxylate. Then, using bromine, the acetyl group of this compound is brominated to give ethyl 1-bromoacetyl-1-cyclopropanecarboxylate. This bromoacetyl compound is then cyclized with benzylamine to give 5-benzyl-4,7-dioxo-5-azaspiro[2,4]heptane. When this compound is reacted with hydroxylamine hydrochloride, the ketone in 7-position is converted to an oxime to give 5-benzyl-7-(hydroxyimino)-4-oxo-5-azaspiro[2,4]heptane. This oxime is reduced with lithium aluminum hydride to give a spiro ring-containing aminopyrrolidine compound, viz., 7-amino-5-benzyl-5-azaspiro[2,4]heptane. When the benzyl group of this compound is eliminated by an ordinary procedure, such as catalytic hydrogenolysis, 7-amino-5-azaspiro[2,4]heptane which is a racemic compound, is obtained When this cleavage of the benzyl group is preceded after the amino group is protected by the reaction of 2-(tert-butoxycarbonylamino)-2-phenylacetonitrile (hereinafter referred to briefly as BOC-ON), 7-tert-butoxycarbonylamino-5-azaspiro[2,4]heptane is obtained.
Sources & evidence
- ORD record
- ord-717fe8628d184b019d7f96c90b9e0f9e
- Source dataset
- uspto-grants-1994_02
- Patent number
- US05286723
Reaction notes
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