Ammonia → HCID 14578469, compound

HRID 1860276Notes

Reaction equation

HRID 1860276 reaction equation
[O:1]1[C:3]2([CH2:8][CH2:7][N:6](C(OCC3C=CC=CC=3)=O)[CH2:5][CH2:4]2)[CH2:2]1.[NH3:19]>>[NH2:19][CH2:2][C:3]1([OH:1])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 13016598Benzyl 1-oxa-6-azaspiro(2.5)octane-6-carboxylate

Product 1

HCID 14578469HCID 14578469, compound

Procedure

The synthesis of 1-oxa-4,9-diaza-spiro[5.5]undecan-3-ones is described in Scheme 8A (see R. D. Clark, J. M. Caroon, D. B. Repke, A. M. Strosberg, S. M. Bitter, M. D. Okada, A. D. Michel, R. L. Whiting, J. Med. Chem. 1983, 26, 855). N-protected 4-methylenepiperidine epoxides like benzyl 1-oxa-6-aza-spiro[2.5]octane-6-carboxylate are opened by heating with a methanolic solution of ammonia to give the corresponding 4-aminomethyl-4-hydroxypiperidine. The spiro-bicyclic nucleus is formed by the following condensation with chloroacetyl chloride. After removal of the benzyloxycarbonyl group with HBr in acetic acid the spiropiperidine is acylated with 4-cyanobenzoyl chloride. The subsequent steps of alkylation with ω-halogenoalkanoates, formation of the amidine, and cleavage of the ester are carried out as described in the previous Schemes.

Sources & evidence

ORD record
ord-4608c2b7d25945d9b246d577b364055d
Source dataset
uspto-grants-2003_03
Patent number
US06528534B2

Reaction notes

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