Novel methods for the synthesis of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]- acetamide ((R)-phenotropil)

M. Vorona; G. Veinberg; S. Vikainis; E. Kuznetsov; A. Lebedev; Yu Ponomarev; A. Chernobrovijs; L. Zvejniece; M. Dambrova

doi:10.1007/s10593-012-1050-y

Novel methods for the synthesis of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]- acetamide ((R)-phenotropil)

M. Vorona, G. Veinberg, S. Vikainis, E. Kuznetsov, A. Lebedev, Yu Ponomarev, A. Chernobrovijs, L. Zvejniece, M. Dambrova

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Two novel methods have been developed for the preparation of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide ((R)-Phenotropil). In the first, n-butyl (3R)-4-amino-3-phenylbutyrate is alkylated with haloacetamide in DMF in the presence of potassium phosphate monohydrate, and the intermediate 4-carbamoylmethylamino-3-phenylbutyrate is subsequently cyclized by refluxing in toluene in the presence of potassium phosphate monohydrate and tetrabutylammonium bromide. In the second, chloroacetonitrile is used under similar conditions in place of the haloacetamide. Both methods lead to (R)-Phenotropil in 40-60% yields calculated on the starting n-butyl (3R)-4-amino-3-phenylbutyrate.

Original language	English
Pages (from-to)	720-723
Number of pages	4
Journal	Chemistry of Heterocyclic Compounds
Volume	48
Issue number	5
DOIs	https://doi.org/10.1007/s10593-012-1050-y
Publication status	Published - Aug 2012
Externally published	Yes

Keywords*

2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl] acetamide
Alkylation
Cyclization
N-butyl (3R)-4-carbamoylmethylamino-3-phenylbutyrate
N-butyl (3R)-4-cyanomethyl-amino-3-phenylbutyrate

Field of Science*

1.4 Chemical sciences

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1007/s10593-012-1050-y

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@article{21e64be095ce48598978010ef4ed5f38,

title = "Novel methods for the synthesis of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]- acetamide ((R)-phenotropil)",

abstract = "Two novel methods have been developed for the preparation of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide ((R)-Phenotropil). In the first, n-butyl (3R)-4-amino-3-phenylbutyrate is alkylated with haloacetamide in DMF in the presence of potassium phosphate monohydrate, and the intermediate 4-carbamoylmethylamino-3-phenylbutyrate is subsequently cyclized by refluxing in toluene in the presence of potassium phosphate monohydrate and tetrabutylammonium bromide. In the second, chloroacetonitrile is used under similar conditions in place of the haloacetamide. Both methods lead to (R)-Phenotropil in 40-60% yields calculated on the starting n-butyl (3R)-4-amino-3-phenylbutyrate.",

keywords = "2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl] acetamide, Alkylation, Cyclization, N-butyl (3R)-4-carbamoylmethylamino-3-phenylbutyrate, N-butyl (3R)-4-cyanomethyl-amino-3-phenylbutyrate",

author = "M. Vorona and G. Veinberg and S. Vikainis and E. Kuznetsov and A. Lebedev and Yu Ponomarev and A. Chernobrovijs and L. Zvejniece and M. Dambrova",

year = "2012",

month = aug,

doi = "10.1007/s10593-012-1050-y",

language = "English",

volume = "48",

pages = "720--723",

journal = "Chemistry of Heterocyclic Compounds",

issn = "0009-3122",

publisher = "Springer New York",

number = "5",

}

TY - JOUR

T1 - Novel methods for the synthesis of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]- acetamide ((R)-phenotropil)

AU - Vorona, M.

AU - Veinberg, G.

AU - Vikainis, S.

AU - Kuznetsov, E.

AU - Lebedev, A.

AU - Ponomarev, Yu

AU - Chernobrovijs, A.

AU - Zvejniece, L.

AU - Dambrova, M.

PY - 2012/8

Y1 - 2012/8

N2 - Two novel methods have been developed for the preparation of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide ((R)-Phenotropil). In the first, n-butyl (3R)-4-amino-3-phenylbutyrate is alkylated with haloacetamide in DMF in the presence of potassium phosphate monohydrate, and the intermediate 4-carbamoylmethylamino-3-phenylbutyrate is subsequently cyclized by refluxing in toluene in the presence of potassium phosphate monohydrate and tetrabutylammonium bromide. In the second, chloroacetonitrile is used under similar conditions in place of the haloacetamide. Both methods lead to (R)-Phenotropil in 40-60% yields calculated on the starting n-butyl (3R)-4-amino-3-phenylbutyrate.

AB - Two novel methods have been developed for the preparation of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide ((R)-Phenotropil). In the first, n-butyl (3R)-4-amino-3-phenylbutyrate is alkylated with haloacetamide in DMF in the presence of potassium phosphate monohydrate, and the intermediate 4-carbamoylmethylamino-3-phenylbutyrate is subsequently cyclized by refluxing in toluene in the presence of potassium phosphate monohydrate and tetrabutylammonium bromide. In the second, chloroacetonitrile is used under similar conditions in place of the haloacetamide. Both methods lead to (R)-Phenotropil in 40-60% yields calculated on the starting n-butyl (3R)-4-amino-3-phenylbutyrate.

KW - 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl] acetamide

KW - Alkylation

KW - Cyclization

KW - N-butyl (3R)-4-carbamoylmethylamino-3-phenylbutyrate

KW - N-butyl (3R)-4-cyanomethyl-amino-3-phenylbutyrate

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U2 - 10.1007/s10593-012-1050-y

DO - 10.1007/s10593-012-1050-y

M3 - Article

AN - SCOPUS:85027938649

SN - 0009-3122

VL - 48

SP - 720

EP - 723

JO - Chemistry of Heterocyclic Compounds

JF - Chemistry of Heterocyclic Compounds

IS - 5

ER -

Novel methods for the synthesis of 2-[(4R)-2-oxo-4-phenylpyrrolidin-1-yl]- acetamide ((R)-phenotropil)

Abstract

Keywords*

Field of Science*

Publication Type*

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