Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
USO05268501A
Ikeda et a1.
[45]
5,268,501
Date of Patent:
[57]
Dec. 7, 1993
ABSTRACT
[73] Assignee:
all of Japan
Sumitomo Chemical Company,
ll
Dec.9, 1992
x/\/\/\/\on
ll
0
[11]
5,202,467.
[30]
[51]
[58]
[52]
Field
US. Cl.
of Search
...... .. ....................................... .. 560/168
[56]
References Cited
ONOR4
[IV]
6/1982
II
[111]
x/\/\/\/\ (ml
ll
OTHER PUBLICATIONS
NOH
3 Claims, N0 Drawings
5,268,501
Page 2
OTHER PUBLICATIONS
5,268,501
ONOR
[IV]
20
.25
(b) process comprising reacting a 1,3-dithiane deriva 35 ters (e.g. 7-halo-Z-carbomethoxyheptanoic acid ester,
7-halo-2-carboethoxyheptanoic acid ester, 7-halo-2-car
tive with a 1,5-dibromopentane (cf. J. Med. Chem. 1987,
bopropoxyheptanoic
acid ester, 7-halo-2-carbobutox
30, 1074).
yheptanoic
acid
ester,
7-halo-2-carbopentyloxyhep
However, these processes are not satisfactory for the
tanoic acid ester, 7-halo-Z-carbohexyloxyheptanoic acid
production of the compounds [I] on industrial scale,
because these processes strictly need to control the
presence of moisture, and in the process (a), the recov
are expensive.
BRIEF DESCRIPTION OF THE INVENTION 45 the B-oxo-acid ester [II] is one of the above diesters,
that is, when R2 is a group of the formula: R03, it is
An object of the present invention is to provide an
preferable that R1 and R3 are the same.
industrially advantageous process for preparing
The nitrosating agent [IV] used in the present reac
haloketo acid derivatives [I] with solving the above
mentioned problems. Another object of the present 50 tion is, for example, nitrous acid alkyl esters (e. g. methyl
invention is to provide novel B-oxo-acid esters [II] and
nitrite, ethyl nitrite, propyl nitrite, butyl nitrite, pentyl
7-halo-2-hydroxyminoheptanoic acid esters [III], which
nitrite, hexyl nitrite, heptyl nitrite, octyl nitrite, nonyl
are useful for preparing the above haloketo acid deriva
tive [I], and a process for preparing these intermediates
5,268,501
S-chloropentyl p-toluenesulfonate.
The B-oxo-acid derivative [VI] includes, for example,
ketone compound for giving a haloketo acid derivative 25 chain alkyl group (e.g. methyl. ethyl, propyl, butyl,
[1] is usually carried out in the presence of an acid. The
pentyl, hexyl, etc.). When the B-oxo-acid derivative V1]
acid may be any conventional inorganic or organic acid
is a malonic acid diester, that is, when R2 in the formula
(e.g. hydrochloric acid, sulfuric acid, nitric acid, acetic
[V1] is a group of the formula: R03, it is preferable that
acid, etc.). The amount of the acid is not necessarily
R1 and R3 are the same.
speci?ed, but is usually 0.001 mol or more, preferably
In this reaction, the halopentane derivative [V] is
0.01 mol or more, to 1 mol of the B-oxo-acid ester [II].
used in the ratio of about 1 mole to 1 mole of the B-oxo
However, when nitrosylsulfuric acid is used as a ni
used acid derivative [VI], but even though one of these
trosating agent, it is not necessary to use additional acid,
mula [V]:
XWY
lvl
'
5,268,501
6
EXAMPLE 4
EXAMPLE 1
tanoate [ll-1].
EXAMPLE 2
25
EXAMPLE 5
A mixture of ethyl acetoacetate [VI-l] (109.3 g),
EXAMPLE 3
55
EXAMPLE 6
5,268,501
M.p.: 36-38 C.
NNR (60 MHz, CDC13) 8 (ppm): 1.1-2.1 (m, 10),
2.3-3.9 (M, 2), 3.5 (t, 2, J=6.0 Hz), 4.3 (q, 2, J=7.0 Hz)
EXAMPLE 10
EXAMPLE 7
25
[1-1].
EXAMPLE 11
35
A mixture of ethyl acetoacetate [VI-l] (260.6 g, 2.0 40 chloropentane (18.6 g) and stirred under re?uxing for
EXAMPLE 9
of l-bromo-S-chloropentane.
Yield: 84.4 % (to ethyl acetoacetate)
Recovery rate (based on 1-bromo-5-chloropentane):
97.7 %
5,268,501
10
0
/\/\/\/H\ I
X
"
OR
[111]
NOH
15
20
25
35
40
45
55
65