Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Process for the preparation of 17-(3-hydroxypropyl)-17-hydroxysteroids

A technology of hydroxysteroids and hydroxypropyl, which is applied in the production of steroids, organic chemistry, bulk chemicals, etc., and can solve the problems of pure products and yield reduction, propynol instability, difficult separation, etc.

Inactive Publication Date: 2010-06-16
BAYER IP GMBH
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] A disadvantage of using prop-1-yn-3 alcohol (propynol) as a functionalized C3 building block is the significant formation of by-products (especially 17-ethynyl steroids) due to its instability to bases
[0011] All in all, the instability of propynyl alcohol can lead to difficulties in the separation of pure products and lower yields

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process for the preparation of 17-(3-hydroxypropyl)-17-hydroxysteroids
  • Process for the preparation of 17-(3-hydroxypropyl)-17-hydroxysteroids
  • Process for the preparation of 17-(3-hydroxypropyl)-17-hydroxysteroids

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0101] 6β, 7β; 15β, 16β-dimethylene-17α-(3-benzyloxypropynyl)androstane-3β, 5β, 17β-triol (Vb)

[0102] According to GWP1, 100 g (0.303 mol) of 3β, 5β-dihydroxy-6β, 7β; -Alcohol benzyl ether reaction.

[0103] The crude product was recrystallized from 700 ml of toluene. 133 g (0.279 mol) of 6β,7β;15β,16β-dimethylene-17α-(3-benzyloxypropyne)androst-3β,5β,17β-triol were obtained (92% yield of theory).

[0104] [α] D 20 =-70.1° (CHCl 3 , 12.15mg per 1ml solution, T=20°C, d=100mm).

[0105] 1 H-NMR (400MHz, CDCl 3 ): δ=0.37-0.42 (1H, m, H-30exo * ), 0.63(1H, td, J=9.0Hz and 5.1Hz, H-31endo), 0.78(1H, q, J=5.1Hz, H-31endo), 0.82-0.88(1H, m, H-6), 0.85 (3H, s, H-19), 0.91 (3H, s, H-18), 1.13 (1H, tt, J=8.4Hz and 4.3Hz, H-7), 1.15-1.27 (4H, m, H -30exo, H-1, H-9, H-11), 1.39-1.44 (1H, m, H-2α), 1.46-1.54 (3H, m, H-11, H-12β, H-15), 1.57 (1H, dt, J=13.6Hz and 2.9Hz, H-2β), 1.66-1.74 (3H, m, H-12α, H-16, H-8), 1.84 (1H, td, J=14.5Hz and 2.9Hz, H-1β), 1.96-2.01 (1H, m, H-4β)...

Embodiment 2

[0110] 15β,16β-methylene-17α-(3-benzyloxypropynyl)androst-6-ene-3β,5β,17β-triol

[0111] According to GWP1, 100 g (0.317 mol) of 3β, 5β-dihydroxy-15β, 16β-methylene-androst-6-en-17-one was mixed with 50.9 g (0.349 mol) of prop-1-yn-3 -Alcohol benzyl ether reaction.

[0112] The crude product was recrystallized from 700 ml of toluene. 134.5 g (0.291 mol) of 15β,16β-methylene-17α-(3-benzyloxypropynyl)androst-6-ene-3β,5β,17β-triol were obtained (92% theoretical yield) .

[0113] [α] D 20 =-120.3° (CHCl 3 , 12.15mg per 1ml solution, T=20℃, d=100mm)

[0114] 1 H-NMR (400MHz, CDCl 3 ): δ = 0.35-0.42 (1H, m, H-30exo), 0.95 (3H, s, H-18), 0.96 (3H, s, H-19), 1.14 (1H, ddd J = 6.8Hz, 3.7 Hz and 3.5Hz, H-30endo * ), 1.28-1.35 (1H, m, H-11β), 1.38-1.42 (1H, m, H-15), 1.45-1.51 (2H, m, H-1β, H-2), 1.50-1.60 (3H , m, H-12β, H-11α, H-9), 1.60-1.65 (1H, m, H-2), 1.67-1.73 (2H, m, H-16, H-12α), 1.83-1.89 ( 1H, m, H-1α), 1.88-1.97 (3H, m, both H-4, H-14), 2.15-2.19 (1H, m, H-8), 2....

Embodiment 3

[0123] 6β, 7β; 15β, 16β-dimethylene-17α-(3-hydroxypropyl)androstane-3β, 5β, 17β-triol (Ia):

[0124] 100 g (0.210 mol) of 6β, 7β; 15β, 16β-dimethylene-17α-(3-benzyloxypropynyl)androstane-3β, 5β, 17β-triol was reacted according to GWP2 or GWP3, 81.1 g (0.208 mol) of 6β,7β;15β,16β-dimethylene-17α-(3-hydroxypropyl)androstane-3β,5β,17β-triol were obtained (99% yield of theory).

[0125] MS(CI): m / e=389(M-H) + , 373 (M+H-H 2 O) + , 355 (373-H 2 O), 337(355-H 2 O), 319(337-H 2 O).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention relates to a process for the preparation of 17a-(3-hydroxypropyl)- 17ss-hydroxysteroids of the formula (I) starting from 17-ketosteroids of the formula (III) via the intermediates of the formula (V) wherein the radicals R3, R5, R6, R7, R10, R13, R15, R16, R40, R41 and R42 have the meaning indicated in the description.

Description

technical field [0001] The present invention relates to a method for preparing 17α-(3-hydroxypropyl)-17β-hydroxy steroid, the intermediate of the method, the preparation method of the intermediate and the use of these intermediates in the preparation of steroid 21,17-spironolactone, especially DR Uses in spirone. Background technique [0002] 17α-(3-hydroxypropyl)-17β-hydroxy steroid of formula I [0003] [0004] As starting material for the synthesis of pharmacologically active steroid 21,17-carboxylides such as eplerenone (9α,11α-epoxy-7α-methoxy-carbonyl-3-oxo-17α-pregna- 4-ene-21,17-carboxylactone), drospirenone (6β,7β; 15β,16β-dimethylene-3-oxo-17α-pregna-4-ene-21,17-carboxylate ester), spironolactone (7α-acetylthio-3-oxo-17α-pregna-4-ene-21,17-carboxylactone), canrenone (3-oxo-17α-pregna-4, 6-diene-21,17-carboxylactone) and plerenone (6β,7β-methylene-3-oxo-17α-pregna-4-ene-21,17-carboxylactone). [0005] The synthesis of these steroid 21,17-spironolactones is c...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07J53/00
CPCC07J53/008Y02P20/55C07J71/0005
Inventor C-C·黑泽尔霍夫M·彼得森
Owner BAYER IP GMBH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com