# US 8,772,490 B2 · Optically active diazabicyclooctane derivatives and process for preparing the same

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- Number: US 8,772,490 B2
- Document ID: US8772490B2
- Status: Granted
- Kind: B2
- Application number: 13/173,002
- Filed: 2011-06-30
- Published: 2012-06-28
- Granted: 2014-07-08
- Earliest claimed: 2010-12-22
- Assignees: Meiji Seika Pharma Co., Ltd.
- Applicants: Takao Abe; Masayuki Okue; Yoshiaki Sakamaki
- Inventors: Takao Abe; Masayuki Okue; Yoshiaki Sakamaki
- Web page: https://patentgrep.com/patent/US8772490B2

## CPC

- C07D 471/08: Bridged systems
- C07D 211/60: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07B 2200/07: Optical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

Provided are an optically active diazabicyclooctane derivative defined by formula (F) below, which is useful as a pharmaceutical intermediate for β-lactamase inhibitor, and a process for preparing the same. In formula (F) above, R1 represents CO2R, CO2M, or CONH2, wherein R represents a methyl group, a tert-butyl group, an allyl group, a benzyl group, or a 2,5-dioxopyrrolidin-1-yl group, and M represents a hydrogen atom, an inorganic cation, or an organic cation; and R2 represents a benzyl group or an allyl group.

## Claims

### Claim 1

An optically active (2S,5R)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid compound of the following formula (F):
wherein
R1 represents CO2R, wherein R represents a methyl group, a tert-butyl group, or a 2,5-dioxopyrrolidin-1-yl group, and
R2 represents a benzyl group or an allyl group.

### Claim 2

A process for preparing the compound of the following formula (F):
wherein
R1 represents CO2R, wherein R represents a methyl group, a tert-butyl group, or a 2,5-dioxopyrrolidin-1-yl group, and
R2 represents a benzyl group or an allyl group,
which comprises subjecting a compound represented by the following formula (E) to intramolecular urea formation, and then subjecting the resultant compound represented by the following formula (F1) to at least one step of the following steps (a) to (g):
wherein Bn represents a benzyl group, and tBu represents a tert-butyl group,
wherein Bn represents a benzyl group, and tBu represents a tert-butyl group,
step (a) for cleaving the ester of formula (F1),
step (b) for converting the compound of formula (F1) to a form of a salt of an inorganic cation or an organic cation,
step (c) for treating the compound of formula (F1) with an acid to convert the compound of formula (F1) to a free acid,
step (d) for performing carbamoylation for the carboxylic acid group of formula (F1),
step (e) for converting the carboxylic acid of formula (F1) to an ester,
step (f) for removing the benzyl group of the benzyloxy group at the 6-position of the compound of formula (F1), and
a step (g) for converting the group at the 6-position of the compound of formula (F1) to an allyloxy group.

### Claim 3

A compound which is selected from the group consisting of
(2S,5R)-tert-butyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate,
(2S,5R)-methyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate, and
(2S,5R)-2,5-dioxopyrrolidin-1-yl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate.

### Claim 4

A crystal of (2S,5R)-tert-butyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate, which exhibits a powder X-ray diffraction pattern having characteristic peaks appearing at lattice spacings (d) of 11.56, 10.96, 6.55, 6.00, 5.79, 5.56, 5.47, 5.25, 4.90, 4.35, 4.23, and 3.86 Å.

### Claim 5

A crystal of (2S,5R)-methyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate, which exhibits a powder X-ray diffraction pattern having characteristic peaks appearing at lattice spacings (d) of 10.39, 5.86, 5.69, 5.34, 4.81, 4.44, 3.98, 3.78, 3.11, 3.03, 2.93, and 2.77 Å.

### Claim 6

A crystal of (2S,5R)-allyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate, which exhibits a powder X-ray diffraction pattern having characteristic peaks appearing at lattice spacings (d) of 14.72, 4.91, 4.46, 4.24, and 3.67 Å.

### Claim 7

A crystal of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid cyclohexylammonium salt, which exhibits a powder X-ray diffraction pattern having characteristic peaks appearing at lattice spacings (d) of 9.95, 8.45, 6.26, 5.87, 5.52, 5.22, 5.10, 4.96, 4.73, 4.54, 4.16, 3.93, and 3.55 Å.

### Claim 8

A crystal of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid, which exhibits a powder X-ray diffraction pattern having characteristic peaks appearing at lattice spacings (d) of 8.19, 7.14, 6.64, 6.29, 5.60, 5.21, 4.91, 4.60, 4.21, 3.69, 3.45, and 3.13 Å.

### Claim 9

A crystal of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide, which exhibits a powder X-ray diffraction pattern having characteristic peaks appearing at lattice spacings (d) of 13.06, 6.52, 5.14, 4.74, 4.63, 4.34, 3.85, and 3.72 Å.

### Claim 10 (depends on 3)

The compound of claim 3, wherein the compound is (2S,5R)-tert-butyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate.

### Claim 11 (depends on 3)

The compound of claim 3, wherein the compound is (2S,5R)-methyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate.

### Claim 12 (depends on 3)

The compound of claim 3, wherein the compound is (2S,5R)-2,5-dioxopyrrolidin-1-yl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate.