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Process for preparing butanetriol derivative

a technology of butanetriol and derivatives, applied in the field of process for preparing butanetriol derivatives, can solve the problems of ozone harmful to human body, high cost of glycidyl trityl ether, and inability to prepare glycidyl trityl ether, etc., and achieve the effect of favorable preparation

Inactive Publication Date: 2004-02-05
DAISO CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This process enables the scalable production of butanetriol derivatives with improved safety and cost-effectiveness, avoiding the limitations of previous methods by using more accessible reagents and conditions, thus facilitating the production of antidiabetic compounds with protein kinase C inhibiting activity.

Problems solved by technology

Glycidyl trityl ether, however is expensive and the reactions with vinylmagnesium bromide and by ozonolysis have to be carried out at lower temperature, -20.degree. C. and -35 to -50.degree. C., respectively.
The procedures, therefore are troublesome.
Furthermore, ozone is harmful to human body and there is a possibility of explosion.
Thus, the known methods are not satisfactory for application to industrially scaled production.

Method used

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  • Process for preparing butanetriol derivative
  • Process for preparing butanetriol derivative
  • Process for preparing butanetriol derivative

Examples

Experimental program
Comparison scheme
Effect test

example 2

[0147] (1) Preparation of (S)-ethyl 3-hydroxy-4-trityloxybutanoate (18) 15

[0148] To (S)-ethyl 3,4-dihydroxybutanoate (1.40 g, 9.45 mmol) in methylene chloride (20 ml) were added triethylamine (1.15 g, 11.36 mmol) and DMAP (17 mg, 0.139 mmol) and the solution was cooled in ice bath. Trityl chloride (2.90 g, 10.4 mol) in methylene chloride (15 ml) was dropped to the solution under stirring and then stirred at room temperature over night. The reaction mixture was washed with saturated ammonium chloride and then saturated brine, dried on magnesium sulfate, filtered and condensed in vacuo. The residue was subjected to silica gel chromatography to give (S)-ethyl 3-hydroxy-4-trityloxybutanoate (1.11 g, yield 31%).

[0149] m.p. 98.8-101.1.degree. C.

[0150] [.alpha.].sub.D.sup.25 -13.1.degree. (C=1.0, EtOAc)

[0151] .sup.1H-NMR (270 MHz, CDCl.sub.3).delta.:1.23(3H, t, J=8.1 Hz), 2.54(2H, q, J=2.7 Hz), 2.94(1H, d, J=2.7 Hz), 3.17(2H, d, J=5.4 Hz), 4.13(2H, q, J=8.1 Hz), 4.22(1H, m), 7.21-7.32(9H, ...

example 3

[0168] (1) Preparation of (S)-4-benzyloxy-l-trityloxy-2-butanol (15) 20

[0169] Sodium hydride (74 mg, 1.85 mmol, 60% in oil) was loaded under argon circumstance in three necked flask and hexane (2 ml) was added thereto. After stirring for a while, it was allowed to stand and the supernatant was removed by syringe. By repeating this procedure three times, the oil of sodium hydride was removed. After drying in vacuo anhydrous dimethyl sulfoxide (DMSO) (2 ml) was added and the solution was cooled to 0.degree. C. (S)-1-Trityloxy-2,4-butandiol (0.62 g, 1.68 mmol) prepared by Example 2-(2) in DMSO (3 ml) was dropped by taking care of the temperature over a one hour period at room temperature to the solution. Then the solution was stirred for 1 hour. To the solution was dropped benzyl chloride (0.213 ml, 1.85 mol) in DMSO (3 ml) over a one hour period at the range of 0.degree. C. to 5.degree. C. and then the solution was stirred for 4 hours. To the reaction mixture was added water (5 ml) an...

example 4

[0172] Preparation of (S)-3-[(2-methylsulfonyloxy)ethoxy]-4-trityloxybutyl methanesulfonate (22) 22

[0173] In toluene (120 ml) were dissolved crude (S)-3-(2-benzyloxyethoxy)--4-trityloxybutanol (29.4 g) without silica gel chromatography prepared in the same method as Example 1, and triethylamine (23 ml, 0.165 mol). To the solution was added portionwise methanesulfonyl chloride (12.2 ml, 0.1575 mol) under ice cooling at the range of 0.degree. C. to 5.degree. C. Then, the solution was stirred at the same temperature for 3 hours. The solution was condensed in vacuo, diluted with ethyl acetate, washed with water and saturated brine, dried on sodium sulfate, filtered and condensed in vacuo to give crude (S)-3-[(2-methylsulfonyloxy)ethoxy]-4-tr-ityloxybutyl methanesulfonate (38.64 g). The crude product was recrystallized twice from a mixture of ethyl acetate and heptane to give purified product (18.15 g, yield 44%).

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Abstract

A process for preparing a butanetriol derivative of the formula (1) useful as intermediates of medicines wherein R<1 >is the same defined below, which comprises reacting a compound of the formula (3) wherein R<1 >and R<2 >are the different protecting groups, and an ethylene glycol derivative in a basic condition to prepare a compound of the formula (4) or (4a) wherein R<1 >and R<2 >are the same defined above, and then subjecting the compound (4) or (4a) to selective deprotection reaction.

Description

[0001] The present invention relates to a process for preparing a butanetriol derivative, which is important as an intermediate in making antidiabetics having protein kinase C inhibiting activity and relates to a novel intermediate of the butanetriol derivative.[0002] Butanetriol derivatives are used as intermediates in making antidiabetics having protein kinase C inhibiting activity. It is known that butanetriol derivatives are prepared by reacting glycidyl trityl ether and vinylmagnesium bromide, by allyl-etherification and by ozonolysis of resulting olefin, followed by treatment of resulting aldehyde with sodium borohydride (U.S. Pat. No. 5,541,347).[0003] Glycidyl trityl ether, however is expensive and the reactions with vinylmagnesium bromide and by ozonolysis have to be carried out at lower temperature, -20.degree. C. and -35 to -50.degree. C., respectively. The procedures, therefore are troublesome. Furthermore, ozone is harmful to human body and there is a possibility of exp...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07B53/00C07C41/16C07C41/26C07C43/178C07C303/28C07C303/30C07C309/66C07F7/18
CPCC07C303/28C07C303/30C07C309/66Y02P20/55C07C43/178
Inventor HIRATA, MAKOTOMIKAMI, MASAFUMIFURUKAWA, YOSHIRO
Owner DAISO CO LTD