JPS6058992A - Silyloxynaphthylbutyl butenoate derivative - Google Patents

Abstract

NEW MATERIAL:A compound of formula I [R1 is 1-3C alkyl; R2 is 1-3C alkoxyl or (substituted) amino; R3 is 1-6C alkyl]. EXAMPLE:Methyl 4-[1'-tertiary butyl-dimethylsilyloxy-4'-hydroxy-5'-methoxy-3'- (5''-oxoheptanoyl)naphtho-2'-yl]-2-butenoate. USE:An intermediate for preparing aclacinomycin which is a carcinostatic agent. PREPARATION:For example, a compound of formula II is reacted with a base in a solvent to give a compound of formula III, which is then reacted with lithium diisopropylamine and then 3-ethylenedioxypentanal to afford a compound of formula IV. The resultant compound is then hydrogenated in the presence of a catalyst in a solvent and heated in the presence of an acid, and then the resultant product is treated with a demethylating agent. The demethylated product is further reacted with methyl 2-dimethylphenylsilyl-3-butenoate to give a compound of formula V, which is then reacted with tertiary butyldimethylsilyl chloride.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel silyloxynaphthyl butenoate derivatives. More specifically, the present invention is directed to a compound of the general formula % (formula %) (wherein R1 is an alkyl group having 1 to 3 carbon atoms) which is useful as an intermediate for the production of acrinomine or its analogues, which are known as anticancer agents. , R2 is an alkoxy group having 1 to 3 carbon atoms, an amino group or a substituted amine group,
R3 is an alkyl group having 1 to 6 carbon atoms).

Aclacinomycin, known as an anticancer drug, is a glycoside of aglucone represented by the formula: Many methods have been proposed to produce this aglucone, but all of them require the formation of carbon rings in sequence, making operations complicated and requiring numerous steps. It had the disadvantage of being necessary. The compound represented by the general formula CI) of the present invention can be easily converted into aglucino/ by treating it with a base, de/lylating it, then oxidizing it, and further oxidizing it after dealkylation. If it is possible to do this, it has the advantage of not only significantly shortening the process but also allowing stereoscopic control.

The compound of the present invention can be produced, for example, according to the steps shown below.

(Ill) 01su(V)(~11) (Vllll (I'1lb C(CH3)3 H2O-Si-CH3 (1) That is, the compound of formula (1) is used as a starting material, and a suitable solvent is added to it. After reacting with a base, a compound of formula (2) is produced by reacting with chlorodimethyl ether.The solvent used in this case is a polar solvent such as dimethylformamide, dimethylacetamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc. is preferred, and the base is preferably lithium hydride, sodium hydride, potassium hydride, sodium hydrogen carbonate, strium carbonate, etc. These bases and chlorodimethyl ether are equivalent to the compound of general formula (1). It is used in an amount of at least 1 mole, preferably 1 to 1.5 times the mole.

Temperatures in the ambient temperature range, preferably from 0° C. to room temperature, are used, and the reaction time is usually about 1 to 10 hours.

Next, the compound of general formula (IV) thus obtained is reacted with lithium diisopropylamine in a suitable solvent, and further reacted with 3-ethylene dioxy/pentanal to form a compound of general formula (V). can get.

As the solvent in this case, cyclic ethers such as dioxane and tetrahydrofuran are suitable. This reaction is -
It is carried out at a temperature from 80°C to room temperature, and the reaction time is usually 1
It takes about 5 hours. Lithium diisopropylamine is used in an amount equal to or more than the equivalent molar amount, preferably 1 to 1.5 times the molar amount of the compound of the general formula (IV). The compound is hydrogenated using a palladium catalyst in a cyclic ether solvent such as dioxane, tetrahydrofuran to give 3-(
5'-ethylenedioxyheptanoyl)-1,5-dimethoxy/-4-7 for several hours using a catalytic amount of an organic acid such as p-toluenesulfonic acid or a mineral acid such as hydrochloric acid. A compound of the general formula (VD) is produced by heat treatment.

Next, the compound of the general formula (Vll) thus obtained is treated with a demethylating agent in a suitable solvent to obtain the compound of the general formula (A). , tetrahydrofuran, etc., and a mixed solvent of water are suitable.

Further, as a demethylating agent, for example, seric ammonium nitrate is used in an excess molar amount with respect to the compound of the general formula (Vfl).This reaction is usually carried out at room temperature for 5 minutes to 2 hours, preferably for 5 to 30 minutes. It is carried out within the range of

A compound of general formula (■) in a suitable solvent in the presence of a Lewis acid,
Reaction with methyl 2-dimethylphenylsilyl-3-butenoate provides compounds of general formula ~II. As the solvent in this case, methylene chloride, chloroform, etc. are suitable, and as the Lewis acid, tin chloride, aluminum chloride, zinc chloride, etc. are suitable. This reaction is
It is carried out for 1 to 5 hours, preferably for 1 to 2 hours, at a temperature of -80°C to o'ct, preferably -78°C to -25°C. Methyl 2-dimethylphenylsilyl-3-butenoate is used in an amount of about equimolar or more, preferably 1 to 1.5 times the molar amount of the compound of the general formula (\'lll).

Finally, the compound of the general formula 0.11) obtained as described above is reacted with tert-butyldimethylsilyl chloride in an appropriate solvent in the presence of a base to obtain a compound of the general formula (
The compound of the present invention of 1) is obtained 3. In this case, polar solvents such as dimethylformamide, dimethylacetamide, and dimethyl sulfokide are suitable as the solvent, and organic tertiary groups such as imidazole and triethylamine are suitable as the base. It is.

This reaction is carried out at a temperature of 0 to 50<0>C, preferably around room temperature, for a period of 1 to 10 hours, preferably for a period of 2 to 611 hours. Tertiary butyldimethylunryl chloride has the general formula (1111
) is used in an amount of 1 to 5 times the mole, preferably 2 to 3 times the mole of the compound.
1 to 5 times the mole of lyl chloride, preferably 1.5 to 5 times
It is used in a 3-fold molar range. This reaction is advantageously carried out in an inert atmosphere, such as in a stream of nitrogen.

The compounds of the invention thus obtained, such as methyl 4-(x'-tert-butyldimethylsilyloxy-4'-
Hydroxy-57-medoxy 3'-(5"-oxyheptanoyl)naphth-2'-yl yo-2-butenoate is usually a pale yellow crystal with a melting point around 110°C, and can be separated from the reaction product by a conventional method. and can be purified.

As described above, the compound of the present invention can be easily converted into akravinone or its analogs by carrying out a cyclization reaction with a base in an appropriate solvent, followed by further desilylation and oxidation. be able to.

Next, the present invention will be explained in more detail with reference to Examples.

Example (1) Production of 3-acetyl-1,5-dimethoxy-4-methoxymethoxynaphthalene; Sodium hydride 3 in dimethylformamide Low/
60 mf (1,5 m mol)' (i711i
The mixture was made cloudy and 2.9% of 3-acetyl-1.5-dimethoxy-4-hydroxynaphthalene was added at 0°C under a nitrogen stream.
50 ml of a dimethyl formaldehyde solution containing 5'6 Li (12 mmol) f was added dropwise while stirring. At this time, the reaction solution changes to an orange/yellow suspension. After the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour, and then 1.15 d of nichlorodimethyl ether was added to the reaction solution, and the mixture was further stirred for 3 hours.

The reaction solution was then poured into ice water, extracted with methylene chloride, washed successively with water, an aqueous solution of sodium bicarbonate and brine, and then dried over sodium sulfate. Next, the solvent was distilled off, and the residue was purified by solica gel column chromatography. In this way, melting point 51.5
Target object 3.075 ? as pale yellow crystals at ~59°C? (
10.6 mmol, yield 88%). The NMR and IR of this product are as follows: O NMR (CDC13); δ = 2.75 (s, 3H)
, 3.38 (s, 3H).

3.94 (s, 6H), 4.98 (s, 2H).

6.90 (s+d, 2H, J=8H2).

7.38 (t, IH, J=8Hz), 7.81 (d, I
H, J = 8Hz).

Engineering R (KBr); 1.665c1n-” (C=O) (
2) Production of 3-(5'-ethylenedioxyhept-2'-enoyl)-1,5-dimethoxy-4-methoxynaphthalene; 1.4 ml of diisopropylamine. In a solution of 10 mmol of lithium diisopropylamine prepared by reacting 10 mmol of n-butyllithium suspended in hexane in a stream of nitrogen, the above 3-acedel-1,5 -dimethoxy-4-methoxymethoxynaphthalene 2.6107
(9 mmol) i A solution 'ff dissolved in 3'0+m of tetrahydrofuran was gradually added dropwise while cooling to -78°C. Next, this mixture was stirred and heated to -20℃ for 1 hour, and after stirring was continued for 30 minutes at this temperature, it was cooled again to 18℃. ? (10,16 mmo
l) Add a solution of f in 5 ml of tetrahydrofuran. Then, the temperature was gradually raised to room temperature and stirred for 30 minutes. The reaction mixture was pressurized into ice water, extracted according to a conventional method, and then subjected to silica gel chromatography (cH2c12
) By purifying using f, the target product 2.754
f (6.61 mmol, yield 73%) is obtained as a brown viscous oil.

The NMR of this product is as follows.

NMR (CDC15); δ+=0.91 (t, 3H
, J=7Hz).

1.65 (q, 211.J = 711Z).

2.59 (m, 2H), 3.40 (s, 3H).

3.84-4.00 (m, 10H).

4.92 (s, 2H), 6.80-6.96 (m, 3
H), 7.36 (t, 2H,, T=7H2), 7.
79 (d, LH, J = 8Hz) (3) 4-hydroxy-
Preparation of 1,5-dimethoxy/-3-(5'-oxoheptanoyl)-naphthalene; the above product 2.725 flf Tetrahydrofuran 2
0rnI! 10% palladium on carbon 400
Add ■ and hydrogenate at room temperature and pressure. After completion of the reaction, the reaction solution was filtered (step 7 to completely remove the catalyst; then, by distilling off the solvent, the crude 3-(5'-ethylenedioxyheptanoyl)-1,5-dimethoxy-4- Methoxymethoxynaphthalene is obtained.Next, it is dissolved in acetone, a small amount of water and a catalytic amount of p-toluenesulfonic acid are added, and the mixture is heated under reflux for about 4 hours.The acetone is distilled off from the reaction solution, and the residue is is extracted with methylene chloride and purified using a silica gel column to obtain the target product 1.770 S' (5
, 35 mmol.

82% yield) is obtained as yellow needles with a melting point of 128-130°C. The NMR and IR of this product are as follows.

NMR (CDC13); δ-1,04(t,3H,J
= 7H2).

2.00 (quint, 2H, J=7H2).

2.49 (q, 2H, J = 7Hz).

3.00 (t+2H, J=7Hz).

3.40 (s, 3H), 3.97 (s, 3H).

6.83 (d, IH, J=8Hz).

6.90 (s, LH), 7.40 (t, LH.

J=8Hz), 7.69(d, LH, J=8Hz), 1
3.10 (S, IH).

IR (KBr): 1695. 1605m' (
C=O)(4) Production of 5-methoxy-3-(5'-oxoheptanoyl)-1,4-naphthoquinono; Dissolve 170 ml of the above product in 40 d of acetonitrile, and add seric ammonium nitrate) 1 .714 r
Add 10+ml of an aqueous solution containing the mixture and stir for 10 minutes at room temperature. Next, add water and methylene chloride to this to separate the liquids,
The aqueous layer is further extracted with methylene chloride. The methylene chloride layers were combined, washed with brine, dried, and then passed through a Nori Gel 7 iodine column (-1).Then, the solvent was distilled off to obtain 461 ml of the crude product. −
When the vines subjected to subsequent reactions up to 1 are purified using solica gel column chromatography (CH2C12),
The desired product is obtained as orange-yellow crystals with a melting point of 94-98.5°C (decomposition). The NMR and R of this product are as follows.
It is a cage.

NMR (CDC13); δ = 1.04 (t, 3H,
J=7H2).

1.95 (quint, 2HIJ-7H2) 12.32
~2.64 (m, 4H).

2.91 (t, 2H, J = 7H2).

3.96 (s, 3H), 6.86 (s, IH).

7.32 (m, IH), 7.60-7.80 (m, 2
H).

Engineering R (KBr): 1690.1650 cm'
(C=O).

(5) Methyl 4-(1'-tert-butyldimethylsilyloxy-4'-hydroxy-57-medoxy3'-(5
"-Oxoheptanoylnaphth-2'-yl)-2-butenoate The above naphthoquinone 987W (3-L4yy+mol
) and 1.06 t (4.31 mmol) of methyl 2-dimethylphenylsilyl-3-butenony) are dissolved in 100 d of methylene chloride and cooled to -78°C. 0.5-'ii of tin chloride is then stirred into this and the yellow solution immediately turns black-purple. The temperature of this was raised to -25°C over 2 hours, water was added, and the oil layer was completely separated using a small amount of ether. Water layer? Extract with methylene chloride, separate the organic layer, wash with brine, and dissolve with sulfuric acid)
Dry with Jum. After distilling off the solvent.

Add ether and hexane and cool to obtain a brown solid material.

1.0405' of the solid thus obtained, 840 μm of tert-butyldimethylsilyl chloride, and 840 μm of imidazole.
'i is dissolved in dimethylformamide 5-, and reacted with stirring at room temperature under a nitrogen atmosphere for 4 hours. Next, this reaction mixture was poured into total water, extracted with methylene chloride, and then subjected to silica gel column chromatography (CH2
C12), the final destination is 1.166 ft'
(yield 70%) is obtained as pale yellow crystals with a melting point of 109-111°C. The NM, T (and IR of this) are as follows.

NMR (CDC15); δ-0,13 (s, 6H),
1.05 (t, 3H.

J=7Hz), 1.06(s, 9H).

1.86 (q, uint, 2H, J'=7Hz).

2.44 (q, 2H, J-7Hz).

2.46 (t, 2H, J=7Hz).

2.94 (t, 2H, J=7H2).

3.65 (d, 2H), 3.67 (s, 3H).

4.03 (s, 3H), 5.65 (d, IH.

J=16Hz), 6.86(d, IH.

J=8H2), 6.96(d+t, LH.

J=16. 7H2), 7.36 (t.

IH, J=8Hz), 7.65 (d, LH.

J='8H2), 9.35 (S, IH).

Engineering R (KBr); 3160 (OH), 1715.
1675. 1645z-'(C=O).

Patent Applicant Asahi Kasei Kogyo Co., Ltd. Agent Yen Form Ming Procedural Amendment Form 1982 8. Whisper 1.16 F] Commissioner of the Japan Patent Office Manabu Shiga 1, Indication of the case, Patent Application No. 1 of 1982 Relationship with the case of a person who does
Asahi Kasei Industries Co., Ltd. Representative Miyazaki A; 1-4, Agent 2-2-2 Shinbashi, Minato-ku, Tokyo Kawasinuma 1-JIX (:”
i building;; floor 6, number of inventions increasing due to amendment ()7
, Target of amendment ar null A product of the invention of the specific store w
1 drawing j8 Contents of correction (1) "Example" in the first line of page 10 of detailed statement f41 will be corrected to "Example 1."

(2) r (0=O) in the 13th line of the 17th page. ”, then add the following sentence on a new line.

“Example 2 In Example 1-(2), 6-acetyl-1,5-dimethoxy-4-methoxymethoxynaphthalene [Compound G
V) The amount of ) was changed as shown in Table 1, and in place of 3-ethylenediogycipentanal), 5,5-ethylenediogyciptanal, 3,3-ethylenedioxy-4-
Methylpentanal and 3,3-ethylenedioxy-4
, 4-dimethylpentanal in the amounts shown in Table 1, and reacted in the same manner as in Example 1-(2) to obtain 6-dimethylpentanal.
(5,5-ethylenedioxy-2-hexenoyl)-
1,5-dimethoxy-4-methoxymethoxynaphthalene (AJ, 3-(5,5-ethylenedioxy-6-methyl-2-heptenoyl)-,1,5-dimethoxy-4-methoxymethoxynaphthalene FB+ and 3 = (5,5
-ethylenedioxy-6,6-dimethyl-2-heptenoyl)-1,5-dimethoxy-4-methoxymethoxynaphthalene (0) was obtained, respectively. Their yields and yields are shown in Table 1.

1 to \ /' / Previously, compounds (A), (B) and (01) were subjected to melting point, NMR, MS, and elemental analysis.The results are shown below.

Compound (A); melting point 107-111°C (ether-hexane recrystallization) NMR (100MHz, aDaz3): δ = 1
．． 73 (3a, ri, 2.64 (2H, m), 14
5 (RoH2Se, 3.97 (3H, El,), 4.Di
(7H, m), 5.01 (2H, su, 6.92-7.0
8 (4H, m), 7.50 (iH, t, J=8H2
), 7.94 (IH, σ.

J=8H2) Engineering R (KBr): 1675.1620.1600.1
570.1365°1265, 1150.1060ar
t'MS: m/e = 403 (M++1.24),
402 (M+, 95).

Roj6 (27), 501 (10υ), 296 (31).

27D56), 257(58) Elemental analysis: CH Theoretical value 65.66% 6.51% ("2□I (as 2607) Actual value 65.39φ 6.61ti compound (B); Melting point 84-85°Q (x-te/I/
-hexane recrystallization) NMR (10 (I MHz, 0DO23): δ = 0
．． 94 (6H,,d, J=7Hz), 1.92(i
H, m).

2.62 (2H, m), 3.22 (3H, s),'
3.94 (6H2su, 3.98 (7H, m), 4.
95 (2H.

6.82-7.00 (4H, m), 7.41 (
IH,t.

J=8Hz), 7.85 (IH, d, J=8Hz)
Engineering R (KBr): 16yo', 1615.1600
．． 1570.1syo.

1270, 1150.1080.1060c1n-”M
S: m/e = 432 (M”+ 2.5), 431 (
M”+1.28).

4,! 10(M, 100), 687(16),
524(16), 616(1a), 3o2(16), 3
0F (89) Elemental analysis, CH Theoretical value 66.96% 7.02% (C24I (as 3o C7)) Actual value 66.82CH 7,24di compound O; melting point 110-112°C (ether-hegisan Base crystal] NMR (100MHz, C!DCz3): δ = 0J8
(9H, S included 27.9 (2H, m), 6.45 (3H
, e), 5.96 (IDE, m), 4.94 (2H.

6.8-7.0 (4H, m), 7.40 (IH
,t.

J=8 Hz), 7.8. ! 1(IH,' d, J=3
H2,) Engineering R (KBr): 1670, 1620, 16
00,1575°137o,1270. 1160.1
065a'MB: m/e=445(M''-1-7,3
3), 444 (M”, 100).

388(23), 387(95L 355(24).

338 (67), 301 (72), 275 (84L23
1 (66) Elemental analysis: . □ Theoretical value 67.55% 7.26% (as 025H3□07) Actual value 67, 4 Q≠ 7.60 Example 1-(6
), 5-(5'-ethylenedioxyhept-
In place of 2'-enoyl) to 1,5-dimethoxy-4-methoxymethoxynaphthalene, the compounds obtained in (1) (Al, (Bl and FCl) were used as shown in Table 2, respectively, Example 1 - React in the same way as (3) and 2, 1,5
-dimethoxy-3-(5-oxohexanoyl)-4-
Naphthol (DJ, 1°5-dimethoxy-6-(6-methyl-5-oxoheptanoyl)-4-naphthol
-oxoheptanoyl)-4-naphthol (t) were obtained, respectively. Their yields and yields are shown in Table 2.

Table 2 For the above compound (D), melting point,
NMR, MS, and elemental analysis were performed. The results are shown below.

Compound: Melting point 117-5 to 118°C (methanol recrystallization) NMR (100Mz, C!DO1!3): δ=2.
10 (2H, quintet, J near H2), 2.
19(jH,s), 2.64(2H,t, J=7H
2).

3.12 (2H, t, J near H2), 4.05 (3
H,'S).

4.11 (3H, e), 7.06 (IH, d, J=
3Hz).

7.19(IH,su, 7.65(IH,t, J=8
Hz).

7.95 (IH, cl, J=8H2), 1141 (
IH, S) Engineering R (KBr) 2 1710. 1625
．． 1600. 1575. 1590°1070C7
n" MS: m/'9 = 317 (M++1. 19), 3
16 (M+, 95).

298 (9), 259 (17), 231 (100)
Elemental analysis: OH Theoretical value 68.34% 6.67% (C18I (2° C5 temperature) Actual value 68.13% 6.38% compound (mole; melting point 83-84°C (methanol recrystallization) NMR (i Do MH2, 0DO7?3) :δ=
1.09 (6H, J J = 7Hz), 2.06 (2H
.

quintet, J=7Hz), 2-2-62 (3
H19゜3.08 (2H, t, J=7Hz), 4.00
(3H, S).

4.06 (3H, s), 6.97 (IH, d, J=8H
z).

7.08 (IH, s'), 7.55 (IH, t, J=8
Hz).

7.83 (IH,' d, J=-8H2), 13.5
0 (IJ B) Engineering R (KBr): 1710,1620
,1605,1580,1390゜101080 J=:m/e== 345 (M++1.22), 34
4 (M”, 97).

259 (30), 246 (65), 231 (100) Elemental analysis: CH Theoretical value 69.75 7.02% (0□.) As 12405] Actual value 69.85% 7.01% Compound (T) ; Melting point 118-119°C (methanol recrystallization) NMR (100Maz, C1DOJ3): δ=
1.14(9H,su, 2.02(2H,quint)
etc.

, T=7H2), 2.64(2H,t, J=7Hz
), 3.05 (2H, t, J Near H2), 3.9
6 (5H, [1), 4.01 (6H, Su, 6.91
(iH, d, J=8Hz), 7.03 (IH, s)
, 7.46 (IH, t, J=8Hz) , 7.76
(IH, (1, J=8Hz), 13.50 (IH, S)
Engineering R (KBr): 1700, 1620, 1600, 1
575,1390°10754' MS: m/e= 359 (M++1.24), 358
(M+, +00).

259 (30), 246 (60), 231 (97) Elemental analysis: . □ Theoretical value 70.57% 7.61% (as C2□H260M) Actual value 70.17S% 7.44% In Example 1-(4), 4-hydroxy-1゜5
-dimethoxy-5-(5'-oxoheptanoyl)-naphthalene, the compound (D) obtained in the above (2), (
(F) and these compounds, acetonitrile and seric ammonium nitrate in the proportions shown in Table 3, and reacted in the same manner as in Example 1-(4) to obtain 5- Methoxy-6-(5-oxohexanoyl)-1,4-naphthoquinone (G), 5-methoxy-3-(6-methyl-5-oxoheptanoyl)-1
, 4-twoftquinone (Isu and 5-methoxy-3-(
Is, +5-di/thyl-5-oxoheptanoyl)-1
, 4-naphthoquinone (1) were obtained. Their yields and yields are shown in Table 3.

Regarding the compounds (G), (b) and fI), the melting point,
NMR.

Engineering R, MS and elemental analysis were performed. The results are shown below.

Compound (G); Melting point 117.5-118°C (ether-hexane recrystallization) NMR (100MHz, 0DG4); δ==
1.94 (2H, quintet, T=7Hz),
2.15(3H*8)', 2.54(2H,t,
J=7Hz).

2.95 (2H, t, J = 7 Hz), 4.0!1 (ro L 8L6.91 (11 (, s), 7.30 (11 (
, m), 7.66 (2H, m) Engineering R (KBr): 1705.1660.1585.1
295°1280, 1215c1n- ME(:m/e==30'l(M"+1.18),
300 (M”, 92).

282 (36), '257 (3B), 243 (85
).

242 (72), 23Q (52), 217 (96)
.

215(95), 187(100) Elemental analysis: . □ Theoretical value 67.99% 5.76% (as CIf H16os) Compound); Melting point 100-108°C (ether-hexane recrystallization) NMR (100MH2,0DO1!s) δ = 1.0
7 ((5H, d, J=7H2), 1,93 (2H.

J = 7 Hz), 2.55 (5
)I, m).

2.92 (2J t, J==7 Hz), 5.99
(3H, 8).

6, B'9 (IJ s), 7.28 (IH, m), 7.
66 (2H, m) Engineering R (KBr): 1700.1665.1585.1
470°1500, 1275.1220 (m = MS: m, /e = 329 (M" + 1.20), 18
(M”, 92).

310 (20), 385 (78), 257 (92)
.

243 (66), 242 (-55), 217 (52
).

215 (100) Theoretical value 69.50 6.14% (as 0, H, oO5) Actual value 69.29% 6.15% Compound (I); Melting point 71-74°C (ether-hexane re- Crystal] NMR (100MH2,0DO73): δ=1.12(
9H, 8), 1.92 (2H, quintet.

J=7 Hz), 2.59(2H,t,' J=7
H2).

2.93 (2H, t, J==7 Hz), 4.00
(3H, s).

6.91 (IJ s), 7.30 (IH, m), 7
．． 68 (2H, m) Engineering R (KBr): 1700.1660.1585.1
470°13QQ, 1280.1230α-1M5.
:m/e=343(M"+1.3), 342(M",
13).

286(100), 285. (51), 258(5
vinegar.

24D48), 215(35) Theoretical value 70.16% 6.47% (0□.As H2205) Actual value 70. Q2% 6.48% In Example 1-(s), 5-methoxy-6-non,
In place of the compound (G) obtained in (3) above, -) and (
1) were reacted in the same manner as in Example 1-(5) under the conditions shown in Table 4 to produce the intermediates (goods), (Nl and (0)) represented by the general formula (2), respectively. methyl 4-(1'-tert-butyldimethylsilyloxy-4
'-Hydroxy-5'-methoxy-3'-(5"-oxohexanoyl)naphtho-2'-ylku-2-butenoate (J), methyl 4-(1'-tert-butyldimethylsilyloxy-4'- Hydroxy-5'-methoxy-31
(6#-methyl-5”-oxoheptanoyl)nando-
2'-Ilk 2-butenoate (K) and methyl 4-
[-,1/-tert-butyldimethylsilyloxy-4'
-Hydroxy-5'-methoxy-3/ (6r/,
6“-dimethyl-5〃-oxoheptanoyl9nando-
21-Ilk-2-butenony) (L) was obtained. Their yields and yields are shown in Table 4.

The pouring equivalent is the value for the compound (■month2).

2) Structure of intermediate 3] Structure of product compound 0 (Q horse) 3 H30-5i-OH3 Said compound [), town (L) and intermediate part), (N), (
0), melting point, NMR1IR% MS, molecular weight measurement, and elemental analysis were performed. The results are shown below.

Compound (J); Melting point 12q-: 1sa°C'MR (100
MH2,0DOz,);δ=0.13(6H,su,
1.06 (9H, s), 1.97 (2H, quint
et, J=7 Hz), 2.14 (3H, S.

2.54 (2H, t, J==7 Hz), 2.9
4 (2H, t.

J=7 Hz), 3.66 (2H, m), 5.68
(5H, s).

4.05 (3H, s), 5.63 (IH, a, J=
16 Hz).

6.85 (IH, d, J=, 8 H2), 6.96
(IH, dt.

J=16.6 H2), 7.36(IH,t,' J
=8H2).

7.65 (IJ d, J==8 HJ, 9.55 (IH
,,s) Engineering R (KBr): 3320.1720. '1
660.1650゜1 (510, 1590, 1430,
1375°1255, 1210 ff” MS: m/e= 516 (M”+2.11), 575
(M″+i, 37).

514 (M”, 100), 496 (i4), 38
3(17).

Molecular weight: Theoretical value 514.2387 (as C28H3807Si) Actual value 514.2342 Intermediate-); Melting point 70-80°C NMR (100Mn2.cDciz): δ" 1.9
8 (2H, quintet, J=7 H2), 1.
17 (3H, 8), 2.4-2.7 (6H, m),
3.69 (3H, []; IH, m), 4.01 (3
H1mL5.70 (iH, eL, J:16 H2),
6.74 (IH.

dt, J=16. B'Hz), 7.35 (IH,
dd.

J=8.2 H2), 7.58 (2H, m), 17.
os (IH, s) Engineering R (KBr): 1720.1690.1660.16
00°1560, 1430.1310', 1270°1210r thin-1 H5: m/e-" 401 (M"+1.25), 400
(M+, 100).

315 (15), 269 (23), 256 (26)
.

255 (20) Elemental analysis: Theoretical value 65.99% 6-04% (C22H2407) Actual value 66.26% 6.07% Compound (K); Melting point 89-90'C NMR (100 MHz, CD (43) :δ=0.
13 (6H, 8), 1.97 (9H, Su, 1.09
(6H, d, J=7 H2), 1.93 (2H,'
quintet.

J==7 H2), 2.5(S(3H,m), 2.
91 (2H, t.

J=7 H2), 3.61 (2H, m), 5.65
C! Jl.

4.02 (3H, S), 5.60 (IH, d, J=
161ELz).

6.7.9 (IH, d , , r==a I(z)
+ 6-89 (IH, dt'+J=16.6 H2
), 7.28 (IH,t, J=8 Hz).

7.58 (1H, d, J=8 H7), 9.2.7 (
IH, Riko R (KBr) = 3400. 1720;
1690. 1650. 1615°1595, 15
80.1380.1270 tm=MS:m/e:=5
44 (M”+2.12), 543 (M++1.40)
.

542 (M”, 100), 524 (20), 44
4(14), 386(24), 671(55),
370 (26) Molecular weight: Theoretical value 542.2699 (as C30H42o, Sl) Actual value 542.2676 Intermediate (field; melting point 81-84°C NMR (100Mn2.0DJ3') 2 δ = 1.0
9 (6H, d, J=7 H2), 1.96 (3H,
m).

2j-2,8(6H,m), 5.66(5H,8;
IH.

m), 3.98 (3H, Li, 5.67 (IH, eL, J
=16'Hz), 6.69(IH, at, J=1
6.8 Hz).

7.2-7.7 (3H, m), 17.05 (IH, Riko R (KBr): 1720.1/i90.1655.
1600.1590°1295, 1270.1210
t - 1M5: m/e = 429 (M''+1.27),
428 (M”, 100).

410(8), 400(11), 315(16),
288 (13), 269 (24), 256 (2s,
255 (19) Molecular weight: Theoretical value 428.1835 /n U Heshi1) Actual value 428.1841 Compound ■; Melting point 105-106°C 11MR (100MHz, CDO/3): δ゛ = 0
．． 12 (6H, s), 1.06 (9J e), 1.
13(9H+ (3L 1.91(2H, quinte
t, J==7Hz), 2.58(2H,t, J=
7 H2), 2.90 (2H, t, J=7 Hz)
, 3.60 (2H, mL3.64 (3H, e), 4
．． 02(3H,su, 5,59(IH,d, J=16
H2), 6.79 (IH, d, J=8 H2),
6.89 (IH, dt, J=16.6 H2).

7.48(1H,t, J==13 I(Z), 7.
58 (IH, d.

J=8 Hz), 9.26 (IH, S) Engineering R (KBr)
: '3400.1720.1700.1690°16
50.1615, 1595, 1385° 1280 (thin-1 H5: m/e== 558 (M++2. 16), 55
7 (M”-N, 41).

556(M”, 10s, 558(40), 444
(29),', 429(12), 402(17),
383 (24), 372 (18L 561 (6s, 3)
39 elemental analysis. □ Theoretical value 66.87% 7.97% (as C3□H4407Si) Actual value 66.59CH 8.25% Intermediate (0); Melting point 110-112°C NMR (100MHz, 0DO73): δ = 1.1
5 (9H, 8), 1.94 (2H, quartet.

J=7 Hz), 2.4-2.7 (6H, m), 6.6
8 (3H, e; IH, m), 4.00 (3H, s),
5,69(IH,(1,J=16Hz),6+75(I
H, dt, J = 16.8 H2), 7-28 (IH, d
d, J=3.2H2)+7.53(2H,m), 17.
15 (IH, S) Engineering R (KBr): 1715,170
0,1690,1655,1600°1585, 13
10,1290. 1265°1205cm-"MS2m/e=443(M"+1.29), 442
(M”, 100).

350(16), 315(15), 2as(14,).

269(21), 257(23), 256(19).

255 (18) elemental analysis C,H Theoretical value 67.86% 6.83% (as 0□5H3o07) Actual value 67+99chi 7.05% ”

Claims (1)

[Scope of Claims] 1 General Formula % Formula %) (R1 in the formula is an alkyl group having 1 to 3 carbon atoms, R2 is an alkoxy group having 1 to 3 carbon atoms, an amino group or a substituted amine group, R
3 is an alkyl group having 1 to 6 carbon atoms) A silyloxynaphthyl butenoate derivative represented by the following. The silyloki/naphthyl winterthenoate derivative according to claim 1, wherein R3 is a methyl group.