JPS62205075A - 13-dioxinone derivative - Google Patents

Abstract

NEW MATERIAL:A 1,3-dioxin-4-one derivative of formula (X is Br, I or alkyl, alkenyl or alkynyl which may be substituted with electron attractive group; R and R' are alkyl or together form alkylene). EXAMPLE:5-Bromo-1,3-dioxin-4-one-2-spirocyclohexane. USE:Synthon, etc., useful for the synthesis of pharmaceuticals, agricultural chemicals, etc. PREPARATION:The exemplified compound can be produced e.g. by reacting 2-spirocyclohexane-1,3-dioxin-4-one with N-bromosuccinimide.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to a novel 1,3-dioxinone derivative, which has 1,3-dioxynone derivatives substituted at the 5-position, which are useful as synthetic chemical synthons for pharmaceuticals, agricultural chemicals, etc. -Relating to dioxin-4-one derivatives.

(Prior Art) 1,3-Dioxin-4-one derivatives produce highly reactive acylketenes upon heating, and these acylketenes can be reacted with incyanates, cyanates, cyanamides or imines to form 1,3-oxazine derivatives. , reacts with amide to produce N-acetoacetyl derivatives, and reacts with ketene acetal to produce 4-pyrone derivatives. These compounds are useful as medicines, agricultural chemicals, intermediates thereof, and the like. As mentioned above, 1,3-dioxin-4-one derivatives have reactivity equivalent to that of acylketenes, and are useful synthons that can be used in the synthesis of moderate compounds in synthetic chemistry, but diketenes also have similar reactivity. It is known to have However, the yield of the target product is generally better when using an acyl ketene than when using a diketene; By using a compound having various substituents, it becomes possible to introduce various substituents into the compound.

Until now, 1,3-dioxin-4 with unsubstituted 5 and 6 positions
-on, and conversely, some compounds are known that have substituents at the 5, 6-positions, or only the 6-position (JP-A-54-106478, JP-A-54-106478, JP-A-54-106478;
172485 No. 1, 61-17580 and 61-
No. 22077, etc.), and as for the 5-substituted product, only the 5-phenyl form is known (JP-A-59-172485).
It is. However, it is not easy to substitute the phenyl group with another group or introduce a substituent into the benzene nucleus of the 5-phenyl compound, and when it is used as a synthon in synthetic chemistry as described above, Its scope of application is self-limited.

The fact that 1,3-dioxin-4-one compounds substituted only at the 5-position have not been known in the past in any form other than the phenyl form, and that the phenyl form is difficult to convert into other substituted forms is due to the difficulty in its synthesis. Much depends on the method and raw material compound.

(Problems to be Solved by the Invention) The present inventors have discovered that 5-substituted 1,3-dioxin- has a wide range of applications and has various possibilities as synthons in synthetic chemistry.
As a result of research aimed at synthesizing 4-one derivatives, the present invention has been completed.

(Means for Solving the Problems) According to the present invention, a 1,3-dioxin-4-one derivative represented by the following general formula is provided.

General formula (wherein,
1 represents an alkylene group that is bonded to each other and integrated.

) Some examples of typical compounds of the 5-substituted 1,3-dioxin-4-one of the present invention are as follows, along with specific synthesis methods thereof.

(In the following examples, the number before the compound is used as the compound number for convenience.) 2-spisasai xan-1,3-dioxin-4-one (
JP-A No. 61-22077, referred to as compound 1b) 50
A mixture of 641 ml of N-bromosuccinimide (NH3) and IQ ml of acetic acid was stirred at room temperature for 6 hours. The reaction solution was diluted with dichloromethane and thoroughly washed with water. After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 634 m9 (69 cm) of hexadioquinine q-2-subi% and sane.

High-resolution MS rrVz C
a1cd C,1H15Br05(M”):306-0
101 (“Br), 308-0082 (Br)-F
ound: 306, 0059 (79Br), 3
08,0060(“Br)-IRu,,,cm,
1760(ah), 1750.1720(CmO)-'
H-NMR (CDC23) δ: 1.18-2.15 (I
Oh, m.

cyclohexyl), 2.18 (3H, s, O
COMe), 4.27 (IH.

d e J =611ze C5-”) e 6.38
(I Ht d * J==611z # C6-H
) - the above compound (430111f/ , 1.4 mm
ot) and triethylamine (15611r9.1.56
A dichloromethane solution (5 mg) of mmoA) was added at room temperature.
Stir for 5 minutes. After diluting with dichloromethane and washing with water, the organic layer is dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting crystals were recrystallized from hexane-ether to give the title compound (1
) to obtain 278 to (80 inches).

Ana l -C m l e d C1put, Br
Os: Cy 43-75: Ht4.49: B
r, 32.34e Found:C,43,72:
H,4,4,O:Br, 32.43. IRu””
L3cyn-': 1735 (CmO,).

'H-NMR (CDCt,) δ: 1.0? -2,3
0 (10H, m, eyclohexyl).

7.40 (11,s, C6-H), MSny'z
: 248(”Br)(M+).

1 m (1,68II, 10mmot), N-'5
i-dosuccinimide (NIS, 2.71, 12
mmot) and acetic acid (30 m/) at room temperature.
Stir for an hour. The reaction solution was diluted with dichloromethane, thoroughly washed with water, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was dissolved in dichloromethane (30 mA) and further diluted with triethylamine (1,37,9°13
, 5 m mot) and stirred at room temperature for 20 minutes. After washing the reaction solution with water, the organic layer is dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting crystals were recrystallized from hexane-ether to obtain 1.97.9 (67%) of the title compound (2) as needle-like crystals with a mp of 97-98°C.

Anal Cal cd CqHl, Eng Os: C
,36,76: He 3.7? -ClO2-1.

Found: C, 36, 56: H, 3, 63, IR
&Im,! cm.

1725 (C=O), 'H-NMR (CDCt
, ) δ: 1.20-2.30 (IOH, m, cycle
ohexyl), 7.37 (IH; a, C6-H).

MS m/z: 294 (M'') -2,2-dimethyl-1,3-dioxin-4-one (same as above, referred to as compound 1a) (128~.

1 mmoL), NBS (215 m9, 1.2 m
A mixture of (molL) and acetic acid (4 mg) is stirred at room temperature for 3 hours. The reaction solution was diluted with dichloromethane, thoroughly washed with water, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, the residue was dissolved in dichloromethane (5 ml), and triethylamine C87m9, 0.86 mmo
Add t) and stir at room temperature for 15 minutes. The reaction solution is washed with water, and the organic layer is dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the title compound (3) was obtained as an oil at 74 W/(3
6 h) obtain.

High-resolution MS m/z
Ca1cd C,H42BrO2(M+): 207.0
019 (Br), 209.0000 (Br), Foun
d: 206.9981 (Br), 208.9907 (B
r).

IH value cm-': 1740 (C=O)-'
H-NNIR (CCl2) δ: 1.73 (6H,s
, MgX2), 7.33 (IH,s, C6-H)
.

1 a (1,311, 10,2 mmot), NIS
(2,76,9°12,3 mmoL) and acetic acid (2
5me) was stirred at room temperature for 5 hours. After diluting the reaction solution with dichloromethane and washing thoroughly with water, the organic layer is dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, the residue was dissolved in dichloromethane (30 ml), triethylamine (1,131, 11 mmot) was further added, and the mixture was stirred at room temperature for 20 minutes. After washing the reaction solution with water, the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel amount: 50
g). Hexane-ethyl acetate (ts:t*v/
v) Compound (4) described as a pale yellow oil from the eluted part
1.8911 (75%) is obtained.

High-resolution MS rrI/z
Ca1cd C6H, IO5 (M+): 253.94
38. Found :253.9448. IRνcH
c"cm-': 1735 (C=O), 'H-NM
R(CC44)δ: 1.72 (6H, 8°MgX2),
7.34 (IH, s, C6-H).

5-halogeno-1,3-dioxin-4-one (0,5
mmot), monosubstituted acetylene (2,5mmot)
, Pd(Ph3P)2Ct2(0,025mmoL')
e A DMF solution (4 m/) of Cu I (0.0-1 mmot) and triethylamine (1 mmol) is stirred in a sealed tube or heated at 60 to 70°C. The reaction solution was diluted with ether, washed with water, and the ether layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by the method described below.a) Compound (1) (124"S
', 0.5 mmot), phenylacetylene (2
55m9, 2.5 mmot), Pd(Ph3P)2
Ct2 (8WIIp O, 01 mmot), CuI (
8m9, 0.04 mmot), triethylamine (
After reacting a DMF solution (4 mJ) of 101m911 mmot) at 70°C for 12 hours according to general procedure A, the ether extracted fraction was subjected to silica gel column chromatography (silica dul amount 2 (17). Hexane-ethyl acetate (2
0:1, v/v) A crystalline substance was obtained from the eluted portion and recrystallized from hexane-ether to obtain mp 101-1.
51 m9 (3
8%). In addition, 42 to (34 inches) of raw materials are also recovered.

Anal Calcd C1, H1603: C, 76
, 10: H, 6, 01.

Found: C@75.95: H, 5, 80*
IRucHcL3m-': 1740 (C=O),
H-NMR (CDCl2) δ: 1.10-2.33
(10H.

m, cyclohexyl), 7.20-7.7
0(6H, m, ArH, C6-H).

MS m/z: 268 (M+).

b) Compound (2) (147"9t 0.5mmoA),
Phenylacetylene (2551nl/e 2.5yy
smoA), Pd(Ph3P)2ct2(18m9
, 0.025 mmot), CuI (811F/,
0.04mmat), triethylamine (10111
IfI, 1 mmot) in DMF solution (4IIA) was reacted at room temperature for 30 minutes according to the general operating corporation, and post-treated in the same manner as a) to obtain the title compound (2) (1,058 g
, 3.6 mmoL), trimethylsilylacetylene (1,761, 18 mmoA), pci (ph3p)
2cz2 (126”!/p O, 18mmot), C
uI (58m9m 0.29mmot), triethylamine (727”/ #7.2 mmoL) in DMF
The solution (281M') was reacted at room temperature for 40 minutes according to the general operating corporation, extracted with ether, and the two fractions were subjected to silica dull column chromatography (silica gel amount: 589). A crystalline substance was obtained from the hexane-ethyl acetate (20:1, v/v) eluate, and recrystallized from pentane to obtain mp7.
873■ of the title compound (6) as needle-like crystals at 3-74℃
(92L) obtained.

Anal Calcd C,4H2,)03Si:
Ct 63.60: He 7.62.

cttct3 ml・Found: C, 63, 30: H, 7, 89e I
Ry, cm.

2160 (C==C), 1740 (C=0), 'H-N
MR (CCl2) δ: 0.22 (9H,a, MgX2
), 1.30-2.30 (IOH, m.

cyclohsxyl) e 7.37 (IH*s
, C6-H)*MS m/z: 264 (M).

Compound, substance (4) (127■, 0.5 mmoA),
1-hexyne (205”9 s 2.5 mmot),
Pd(Ph3P)2Ct□(18m9e0.025mm
ot), CuI (8m9.0.04 mmot),
A DMF solution (5 ml) of triethylamine (101”!/61 mmot) was added at room temperature for 1 hour according to the general operating company.
．． The reaction was allowed to proceed for 5 hours, and the ether extracted fraction was subjected to silica column chromatography (silica gel amount: 129).

From the fraction eluted with hexane-ethyl acetate (20:1), 76-(73%) of the title compound (7) was obtained as a pale yellow oil.

High-resolution MS rrv/z
Ca1cd C,2H,60,(M”) :208.1
100. Found: 208.1122. IR
y""cIn-': 1730 (C=O), 'H-
NMR (CC14) δ: 0.73-1.67 (7Hs
m*Me(CH2)2cu2c==c) p1.
72 (6He s tMeX2) t2.00-2.
83 (2H, m, Me(CH2)2CH2C=C
), 7.27 (I Hv se C6-) I)
.

8) 2.2-methyl-5-trimethylsilylethynyl-1,3-dioxin-4-one compound (4) (127t%F, 0.5mmot)
) Limethylsilylacetylene (24511g, 2.5
mmot).

Pd(Ph3P)2CL2 (18j'li', 0
．． 025mmoL), Cul(8m?, 0.025mmoL), Cul(8m?, 0.
04mmol), ) ethylamine (101#.

A DMF solution (5 ml) of 1 mmot) was reacted for 35 minutes at room temperature according to general procedure A, and the ether extracted fraction was subjected to silica gel column chromatography (silica gel i6 g).
Attach to. Hexane-ethyl acetate (25:1, V/
V) The title compound (8
) gets 99IQ (88chi).

Hlgh-resolution MS m/z Ca
1cd C1, H460, Si (M+): 224.08
67, Found: 224.0864. IRy:”,'
,,'c@-' :2160(CmiC), l 74
0 (C=0), 'H-NMR (CCl2) δ: 0
．． 21(9HtssMe5Si)el, 75(6H,l
, MgX2), 7.33 (I H#a*C6-H
) - Compound (4) (127m?, 0.5mmot)
, Grono 4 Rugyl Alcohol (140~m 2.5mm
ol).

Pd(Ph3P)2Ct2 (18mg, 0.025m
mot), CuI (8m9pO,04mmo
t), ) ethylamine (10lay.

A DMF solution (1 mmot) was reacted at 60°C for 50 minutes according to the general procedure AK, and the ether extracted fraction was subjected to silica gel column chromatography (silica gel il
o, F). Hexane-ethyl acetate (2: l,
v/v) From the eluted portion, 43η (47%) of the title compound (9) was obtained as a pale yellow oil.

High-resolution MS mHz Ca
1cd C, Hl, )04(M+) :182.058
0, Found:182.0590, IR,C
HC4c, -1:3600 (HCCa), 3450 (
OH), 1735 (C=0).

' H-NMR (coct3) δ: 1.75 (6H, a
, MgX2), 3.08 (IH, bra, OH),
4.45 (2H,brs,CH,,OH),
7.40(IHeaeC,s-H)-[5 of compound (2), (4)) and monosubstituted olefin
-Iodo compound (2) and (4) (0,5m m
at ) and monosubstituted olefin (1m mat ),
Pd(OAc)2(0.05m mot), Na
HCO3 (1,25 mmol) tetrabutylammonium chloride (NBu4Ct), 0.5 mmol
A DMF solution (7 ml) of
React at 0'C. The reaction solution was diluted with ether, washed with water, and the ether layer was dried over anhydrous magnesium sulfate. The solvent is distilled off under reduced pressure, and the residue is purified by the method described below.

Compound (2) (147111fi, 0.5mmot
), ethyl acrylate (100W, 1mmot)
, Pd(OAc)2 (1119°0.05mmot)
, NaHCO, (1059,1,25mmot).

NBu4C2 (139119, 0.5 m mot) was reacted for 1 h according to general procedure B, and the ether extracted fraction was subjected to silica gel column chromatography (silica gel!-
5g) Attach d. Hexane-ethyl acetate (10:1,
v/v) A crystalline substance was obtained from the eluted portion, and recrystallized from hexane to obtain the title compound (90 to (67) of 10) as scaly crystals with a mp of 67°C.

Anal, Ca1cd C,4HB305: C,6
3,15;H,6,81-(3H,t*J=7H
z, OCH2Mri, 1.13-2.27 (10H
-m.

(IH, s, C6-H), MS mHz: 168
(M+-C3H60).

-one compound (4) (254W9, 1mmot), ethyl acrylate (200m9, 2mmot), Pd(O
Ac)2(22J19.0.1mmol), Na
HCO3 (2101119m 2.5mmoL), NB
A DMF solution (12 m/) of u4C1 (2781rr9.1 mmot) was reacted for 1.5 h' according to general procedure B, and the ether extracted fraction was subjected to silica gel column chromatography (silica gel ts9). A crystalline material was obtained from the fraction eluted with hexane-ethyl acetate (7:1, v/v), and recrystallized from hexane to obtain 151 μm (67%) of the title compound as a grism with a mp of 64-65°C.

Anal, Calcd C,, H1405: C, 58
, 40; H, 6, 24.

Found: C+ 58-48; H* 6-3
6-IRI'cH"cm-': 1735 #
1700 (C=O), 'H-coct, )δ:
1.28 (3H,t.

6.60 J = 7 Hz, OCR2M@), (2
H, ABq, J=16Hz, CH=7.07
□CHCO), 7.
32 (LH,s, C6-H), MS mHz
:226(M+).

12) @-2,2-dimethyl-5-(3-phthalimido-1-broynyl)-1,3-dioxin-4-
compound (4) (254!19, 1 mmot),
N-7lyl 7-talimide (3741119, 2mmot
), Pd (OA c )2(22”9+0.1 m
mot), NaHCO3 (210'? + 2.5゜mmot), NBu CL (2781119t 1
5. DMF solution (12#111?) of Mmot) according to general procedure B. sh reaction, and the ether extracted fraction was subjected to silica gel column chromatography (silica gel amount io
g).

A crystalline substance was obtained from the hexane-ethyl acetate (5:1, v/v) eluate, and recrystallized from hexane-dichloromethane to give the compound (2) as scaly crystals with a mp of 148-149°C. 5011Ig (16%) was obtained.

Anal, Calcd C,7H,5No5: C,6
5,17:H, 4,83:N, 4.47. Found
:C, 65, 36:H, 5, 13:N, 4.41゜I
RycH"3ays""': 1770, 1735 (
sh), 1710 (C=O).

ax 'H-NMR (CDC2,) δ: 1.68 (6H,
s, MgX2).

4, 35 (2H, d, J = 5 Hz - NCR2
CH=CH) -6,08 (I H, d, J = 16
Hz, NCR2CH=CH), 6.50 (I
H.

d t , J =5.16 Hz, NCR2CH=C
H) -7,17 (I H.

s, C6-H), 7.57-8.07 (4H, m, Ar
H), MSrrv'z: 255 (M+-03H6
0) - Compound (4) (127 mg + 0.5 mmo
L), acrolein diethyl acetal (130m
9+ 1mmot)+Pd(OAe)2 (1119,
0.05 mmot), NaHCOs (10511!9.
1.25 mmot), NBuaCt (139”9.

4.0.5 mmot) in DMF solution (6x/) according to general procedure B. sh reaction, and the ether extracted fraction was subjected to silica gel column chromatography (silica gel amount: 6JF).
) with K-t. Hexane-ff[fkc3:1゜v/v
) The compound described as a yellowish brown oil in the eluted area (to)
31! (24ts) obtained.

IRν: Fu513 Confucian-': 1725 (C=0),'H
-Mako ■Yu, ) δ: 1.23 (6H, t, J=7
Hz, (OCR2Me)X2).

1.70 (6H, s r Me X 2 ) + 2
．． 50 (3H, s + MeC=C) t4.12(
4H, q, J=7Hz, (OCR2Me)X2)
, 7.00 (l H, s, C6-H), MSm
/z: 256 (M+).

14) 2.2-&methyl-5-ethoxylic is nylethyl-compound αO (24m9, 0.106 mmo
Pd-C (6
) and subjected to catalytic reduction in a hydrogen stream. After hydrogen absorption has stopped (30 minutes), Pd-C is removed from the furnace. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel! 2.5 g). The fraction eluted with hexane-ethyl acetate (5:1, V/V) gave 18 m9 (74 m) of the title compound α→ as an oily substance.

High-resolution MS mHz Ca
l cd C11H1605 (M+) :CHCj3
-1.

228.0998. Found: 228.0999.
lR11,,! cm.

1720.1715 (sh) (C=O) -'H-
NMR (CCl2) δ: 1, 23 (3H, t, J
=7 Hz, 0CR2Me), 1.63 (6H
.

s 1Me X 2 ) , 2.43 (4H, s ,
CH2CH2C0) , 4.06 (2H,q, J=
7Hz, OCR2Me), 6.93 (IH,s.

a) Compound (6) (10611#9, 0.4 mm
ot) in tetrahydrofuran solution (IM at 3 mA)
NB u a F tetrahydrofuran solution (0.4x/
) while stirring while cooling with refrigerant, immediately add ether and wash with water. After drying the ether layer over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel amount: 4.5 g). A crystalline substance was obtained from the hexane-ethyl acetate (7:1, v/v) eluate and recrystallized from hexane to give mp
33 of the indicated compound α as needle crystals at 87-87.5°C.
mg (43 g) is obtained.

Anal, Ca1cd C11H1203: C, 6
8,74:H, 6,29.

Found: C, 68,80a, H, 6,04,
IRI/cH"3cIn-': 3300 (C=CH'
), 1735 (C=0'), 'E-NM
R(CDCl2)δ: 1.12-2.28 (IOH, m
, cyelohexyl), 3.10 (IH,s,
C=CH), 7.53 (IH,s,Cb-H)
-MS mHz: 192 (M+).

b) Compound (6) (106In9.0.4 mmot
) DMF solution (4Ill) KFK・2
A solution of H2QC (38 mg, 0.4 mmot) in DMF (1,51 nA-H20 (0.5 m)) was added while stirring under ice-water cooling, and immediately ether was added and washed with water. After drying the ether layer over anhydrous magnesium sulfate, the solvent was removed under reduced pressure. After evaporation, the resulting product was recrystallized from hexane to obtain 68 m (89%) of the title compound (g).

16) 2,2-dimethyl-5-ethynyl-1,3-
Dioxin-4-one compound (8) (85m9, 0
．． FK was added to a DMF solution (3a/) of 38 mmol
・DM of 2H20 (36M9, 0.38 mmot)
A F (2rnl)-H2O(1rrtl) solution is added while stirring under cooling with ice water, and immediately ether is added and washed with water. After drying the ether layer over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel amount: 4 g).

From the hexane-ethyl acetate (7:1, v/v) eluted portion, the indicated compound QQ at mp 54-55°C was extracted with 44II.
1 g (76%) obtained.

High-resolution MS rrV'z
Caled C6HBO3 (M”): 152.04
72. Found: 152.0452. IRνcH
c'3c*-': 3300 (C=CH), 1740 (C
=O), 'H-NMR (CCl2) δ: 1.72 (6
H,s, MeX2), 2.98 (IH,s, C=
CH).

Yu...! ”, my father is burnt.

Compound (to) (192ffi + 1 mmot) in ethyl acetate solution (7at) Pd-C (201ff9
) and subjected to catalytic reduction in a hydrogen stream. After hydrogen absorption has stopped (15 minutes), Pd-Ct-ip is removed. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel amount: 10 g). A crystalline substance was obtained from the hexane-ethyl acetate (20:1 + v/v) eluted portion, which was recrystallized from 4 tons to give the title compound (b) as needle-shaped crystals with a temperature of 169 m9 (86 m9). %)
obtain.

Anal, Calcd C,, H1603: C, 67
, 32: It 8.22-Found: C, 67,
17:Hr 8.17. IRI/""3m-': 1
720 (C=O), 'H-NMR (CCl2) δ:
1.07 (3H, t, J=7Hz, CH2Me), 1
．． 33-2.43 (IOH, m.

6yclohexyl), 2.16 (2H+dq
rJ=1, 7Hz.

CH2Me), 6.79 (IH,t, J=
IHz, C6-H), MSm/z: 196 CM
") - Add pac-c (21 mq> to an ethyl acetate solution (7a/) of compound Q* (201+, 1.37 mmol) and subject it to catalytic reduction in a hydrogen stream. After hydrogen absorption has stopped ( 20 minutes), Pd-C is removed in the oven. The solvent is distilled off under reduced pressure, and the resulting residue is subjected to silica gel column chromatography (silica gel amount: 6 g). Elution with hexane-ethyl acetate (5: 1, v/v). 1797119 (84%) of the title compound alpha frame is obtained as a partially distilled oil.

High resolution MS rn/z C
a1cd C3I1120! , (Fl'l+) :15
6.0785, Found: 156.0783
．． IR1/cH"3m-': 1720 (C=0)
, 'H-NMR (CCl2) δ: 1.1°0 (3)
t.

t l J=7H19CH2Me ) 11.63 (
6H1B, MeX2) 12.18 (2H, q, J=
7H2, CH2Me), 6.78 (IH.

Compound (2) (118 m, 0.4 mmot) and allyltrimethylsilane (686 m, 9.6 mmot) in anhydrous acetonitrile solution B (50 ml) were irradiated with a 100 W high-pressure mercury lamp for 5 hours using a Pyrex filter.
>300 nm). The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel P410 g). Hexane-ethyl acetate (1s
: 1. v/v) 43 m (52%) of the title compound α was obtained as an oily substance from the eluted portion.

High-resolution MS mHz C
a1cd Cl2H1603 (M+): 208.11
00. Found: 208.1103. IRνc
Hc"m-': 1720 (C=O), 'H→dish (CDC
t,) δ: 1.20-2.30 (10H+m, cycle
ohexyl ) + 2.97 (2H+ddd +
J=1.4, 2.8, 6H2, CH2=CHCH2
-), 4.89-5.40 (2H, m, cH2=cnc
H2-), s, 51 (xn, adt, J=6.9,
16Hz, CH2=CHCH2-), 6.87 (IH,
t.

J = 1.4 Hz + 06-H).

Potassium tart-butoxide (2,24,5',
20mmot) in trimethylformamide solution (40ff
tert-butylformyl acetate (2,889, 20 mmot) was gradually added to the mixture under cooling with cryogen and stirring. Add iodomethane (3-109+2
2 mmot) was added at once and stirred at this temperature for 2 hours and then at room temperature for 10 minutes. Add water, make weakly acidic with 10% HCl, and extract with ether. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Dissolve the residue in ether and add cold 2.5% aqueous sodium hydroxide solution (IQ#
+J) three times and wash the alkaline layer with ether. 1
Acidify with 0% HCl, extract with ether, and wash with saturated saline. After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (silica gel amount: 30 g). Tert-butyl 12-methylformyl acetate was extracted as an oil from the hexane-ethyl acetate (20:1, v/v) eluate.
85In9 (15qlJ) is obtained.

11tνcH""cm-': 1715.1690(
C=O).

' H-NMRCC14) δ: 1.23 (3HX
215. d, J = 7Hz.

MeCHCO2), 1.52 (9H, s, O
tert-Bu), 1.63 (3HX315.s,
MeC=CHOH), 3.22 (I HX215
．． dqtJ = 2.7 Hz, MeCHCO2)
, 6.92 (IHX315.d, J=12 Hz,
MaC=CHOH), 9.68 (I HX 2
15. d, J=2Hz.

HCO), 11.35 (IHX315, d, J=1
2Hz.

MeC=CHOH).

Sem1 carbazone: mp 126-1
28℃ (ether-hexane) Anal, Calcd
C7H17N504: C, 50,22:H, 7,9
6:N,, 19.52. Found: C, 50, 2
4:H, 8,16:N.

19.51° To the above compound C316mC516m9r2, add acid anhydride (612m, 6 mmol) and then acetone (232mp, 4 mmot) under cooling with cryogen, and gradually add concentrated sulfuric acid (196ff, 9.2 mmot) while stirring. After stirring for 5 minutes, stir in ice water for 30 minutes and further at room temperature for 30 minutes. Pour into aqueous sodium hydrogen carbonate solution and stir until the acetic anhydride odor disappears. The reaction solution was extracted with ether, and the ether layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (9 g of silica gel). From the fraction eluted with hexane-ethyl acetate (5:1, v/v), 5.0 ml (18%) of the title compound (a) was obtained as an oil.

High-resolution MS m/z Ca
1cd C, H1005 (M”): 142.0628
．． Found:142.0627. IRJ/c
m.

1720 (C=O), 'H-NMR (CDC/1
．． , ) δ: 1.6B (6H.

s, MeX2), 1.76, (3H,s, C5-M
e'), 6.87 (IH.

s, C6-H).

As is clear from these synthetic examples, the 5-position monosubstituted 1
．． 3-dioxin-4-ones are monosubstituted at the 6-position and
．． There is also a compound obtained by treating tert-butyl ester of β-keto acid with acetic anhydride in acetone in the presence of concentrated sulfuric acid similar to the 6-position disubstituted 1,3-dioxin-4-ones ( For example, for compound 20), since this method does not have a good yield, it is usually used for compound 1.
First, using 3-dioxy-4-ones as a starting material,
A method is used in which a brominated or iodized product is obtained, which is further subjected to a cross-coupling reaction using a palladium compound as a catalyst, to selectively introduce a carbon substituent into the halogen substitution site. Regarding cross-coupling reactions with acetylenes, Yamanaka et al. (Chem, Pharm.

Bull, 26.3843 (1978), 5ynt
hesis, 312 (1983)), Ca5sar et al. [J, Organomet, Chem-+93.25
3 (1975)], Hack et al. [ibid. 259), Ogiwara et al.
Tetra hedron 1*tt, +4467
(1975) rSynthesis 777, (
1977) ), and regarding the reaction with the amount of olefin, Heck et al.
, 37, 2320 (197-2)), Yamanaka et al. [
Chem, Pharm, Bull, 30, 364
7 (1982), 27.193 (1979)),
”!effery et al. (J, Chem, Soc, *Che
Although there are reports such as ``M, Commun, 1287 (1984),'' dioxinone rings are generally unstable to heat, so it is necessary to devise a method that allows the reaction to proceed rapidly even at relatively low temperatures. This is desirable.

Furthermore, as shown in the synthesis of Compound 19, there is also a method that utilizes a photoreaction.

The 5-substituted 1,3-dioxin-4-ones thus obtained are, as described above, other known 1,3-dioxin-4-ones.
Like ons, it is used as a synthon in various synthetic chemistry.

House Negro　Ayu #I electrician grandson ゐglaze Beil! , (Funaki 1 @ Shizuki-

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, , R' is a lower alkyl group or R and R
′ represents an alkylene group that is bonded to each other and integrated. ) A 1,3-dioxin-4-one derivative represented by