CN105669608A - Preparing method of (S)-3-hydroxy tetrahydrofuran - Google Patents
Preparing method of (S)-3-hydroxy tetrahydrofuran Download PDFInfo
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Abstract
The invention provides a preparing method of (S)-3-hydroxy tetrahydrofuran, which comprises the following steps: (1) adding (S)-4-Cl-3-hydroxy ethyl butyrate, potassium carbonate, benzyl chloride and DMF into a tri-opening bottle, stirring, refluxing, reducing pressure, standing, drying after washing, and recrystallizing; (2) adding tetrahydrofuran and sodium borohydride into a tetra-opening bottle; stirring and dropwise adding (S)-4-Cl-3-benzyloxy ethyl butyrate, continuing to stir, performing rotary evaporation condensing, cooling, neutralizing after stirring, extracting, and rectifying after rotary evaporation condensing; (3) adding (S)-4-Cl-3-benzyloxy-1-butanol, water and concentrated hydrochloric acid into a tri-opening bottle, starting stirring, heating, then performing temperature preserving reaction, neutralizing, extracting, and distilling after rotary evaporation condensing; (4) dissolving (S)-3-benzyloxy tetrahydrofuran in tetrahydrofuran, adding palladium carbon, introducing hydrogen, stirring to react, filtering, concentrating under reduced pressure, adding the recrystallized product, filtering after icy bath cooling, and drying to obtain the (S)-3-hydroxy tetrahydrofuran. The intermediate product is easy to separate and the yield is higher.
Description
Technical field:
The present invention relates to medicine intermediate field, the preparation method particularly relating to one (S)-3-hydroxyl tetrahydrofuran.
Background technology:
Constitute the nucleotide of Life Base material, aminoacid and monosaccharide and be respectively provided with Chiral properties, the biomacromolecule nucleic acid, protein and the saccharide that are made up of them are respectively provided with characteristic space structure, this characteristic has established the basis that life generates and evolves, and also to have determined chiral material critical role in pharmaceutical science. At present, chiral drug has become as a main trend of pharmaceutical industry development with the character of its uniqueness, synthesizes single optical activity medicine and has become as important goal and the means of chiral drug research. Such as, (S)-3-hydroxyl tetrahydrofuran is the important intermediate of synthesis treatment AIDS-treating medicine-amprenavir, in pesticide, after introducing (S)-3-hydroxyl tetrahydrofuran group, activity of weeding and the selectivity of diphenyl ether herbicide can be significantly improved.
At present, (S) preparation method of-3-hydroxyl tetrahydrofuran mainly has two kinds: the reduction of (1) malic acid-molecule inner ether is combined to, utilize L MALIC ACID for initiation material, the major defect of this method is that the lithium aluminium hydride reduction of needs costliness is to reduce malic acid diester, preparation cost is higher, and by-product is more, productivity is less desirable; (2) with (S)-ethyl 3-hydroxybutanoate for raw material, with oxolane-sodium borohydride reduction system, dehydrochlorination Cyclization (S)-3-hydroxyl tetrahydrofuran in acid condition again, simple to operate, route is shorter, but there is also defect: containing hydroxyl in reduzate, water solublity is bigger, the difficulty of extract and separate is relatively big, reduces yield.
Publication number is CN102477019A, publication date is 2012.05.30, apply for the Chinese patent of artificial Suzhou Chireach Biomedical Technology Co., Ltd. discloses " a kind of new method preparing S-3-hydroxyl tetrahydrofuran ", disclose the novel preparation method of a kind of important medicine, pesticide intermediate-S-3-base oxolane, from raw material S-4-chloro-3-hydroxyl ethyl n-butyrate., through hydroxyl protection, reduction reaction, cyclization, protective reaction obtain target product;Using this synthetic method target product optical purity high, good yields, operation is easy, technique environmental protection, is suitable for industrialized production. But, the method there is also certain problem: what hydroxyl protection adopted is alkylation, and intermediate product separating difficulty yet suffers from, and deprotection degree is not high enough, causes that actual recovery is not high.
Summary of the invention:
The present invention to solve the preparation method that the technical problem wanted is to provide one (S)-3-hydroxyl tetrahydrofuran, and intermediate product is easily isolated, and yield is higher.
Want above-mentioned technical problem for solving, the technical scheme is that
A kind of preparation method of (S)-3-hydroxyl tetrahydrofuran, its step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF are added in there-necked flask, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in four-hole bottle, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) chloro-for (S)-4-3-benzyloxy-n-butyl alcohol, water, concentrated hydrochloric acid are added in there-necked flask, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, passing into hydrogen under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, adds 100ml water recrystallization, and ice bath filters after cooling down 1 hour, filter cake is placed in vacuum drying oven dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
Preferably, in step of the present invention (1), the weight ratio of (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF is (85-90): (80-85): (60-65): (350-356).
Preferably, in step of the present invention (1), the capacity of there-necked flask is 1L.
Preferably, in step of the present invention (2), the weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of oxolane, sodium borohydride, (S)-4-is (444-450): (34-35): (110-115).
Preferably, in step of the present invention (2), the capacity of four-hole bottle is 1L.
Preferably, in step of the present invention (3), the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-, water, concentrated hydrochloric acid weight ratio be (100-105): (290-300): (11.5-12).
Preferably, in step of the present invention (3), the capacity of there-necked flask is 1L.
Preferably, in step of the present invention (3), (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be (0.9-1): (72-73): (0.6-0.8).
Preferably, in step of the present invention (4), the baking temperature of vacuum drying oven is 80 DEG C.
With with have technology with than, the method have the advantages that
Hydroxyl has been protected by the present invention by benzyl; the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-generated is easy to separate from reactant liquor; and the deprotection reaction ratio of benzyl is more thoroughly, deprotection degree is higher, and therefore the total recovery of whole preparation method is higher.
Detailed description of the invention:
Describing the present invention in detail below in conjunction with specific embodiment, illustrative examples and explanation in this present invention are used for explaining the present invention, but not as a limitation of the invention.
Embodiment 1
(S) preparation method of-3-hydroxyl tetrahydrofuran, its step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF that weight ratio is 85:80:60:350 are added in the there-necked flask of 1L, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in the four-hole bottle of 1L, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, oxolane, sodium borohydride, (S) weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of-4-is 444:34:110, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-that weight ratio is 100:290:11.5, water, concentrated hydrochloric acid are added in the there-necked flask of 1L, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be 0.9:72:0.6, hydrogen is passed under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, add 100ml water recrystallization, ice bath filters after cooling down 1 hour, and filter cake is placed in vacuum drying oven at 80 DEG C dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
Embodiment 2
(S) preparation method of-3-hydroxyl tetrahydrofuran, its step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF that weight ratio is 86:81:61:351 are added in the there-necked flask of 1L, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in the four-hole bottle of 1L, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, oxolane, sodium borohydride, (S) weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of-4-is 445:34.2:111, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-that weight ratio is 101:292:11.6, water, concentrated hydrochloric acid are added in the there-necked flask of 1L, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be 0.9:72:0.7, hydrogen is passed under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, add 100ml water recrystallization, ice bath filters after cooling down 1 hour, and filter cake is placed in vacuum drying oven at 80 DEG C dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
Embodiment 3
(S) preparation method of-3-hydroxyl tetrahydrofuran, its step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF that weight ratio is 87:82:62:352 are added in the there-necked flask of 1L, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in the four-hole bottle of 1L, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, oxolane, sodium borohydride, (S) weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of-4-is 446:34.4:112, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-that weight ratio is 102:294:11.7, water, concentrated hydrochloric acid are added in the there-necked flask of 1L, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be 1:73:0.8, hydrogen is passed under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, add 100ml water recrystallization, ice bath filters after cooling down 1 hour, and filter cake is placed in vacuum drying oven at 80 DEG C dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
Embodiment 4
(S) preparation method of-3-hydroxyl tetrahydrofuran, its step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF that weight ratio is 88:83:63:354 are added in the there-necked flask of 1L, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in the four-hole bottle of 1L, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, oxolane, sodium borohydride, (S) weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of-4-is 448:34.6:113, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-that weight ratio is 103:296:11.8, water, concentrated hydrochloric acid are added in the there-necked flask of 1L, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be 1:73:0.6, hydrogen is passed under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, add 100ml water recrystallization, ice bath filters after cooling down 1 hour, and filter cake is placed in vacuum drying oven at 80 DEG C dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
Embodiment 5
(S) preparation method of-3-hydroxyl tetrahydrofuran, its step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF that weight ratio is 89:84:64:355 are added in the there-necked flask of 1L, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in the four-hole bottle of 1L, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, oxolane, sodium borohydride, (S) weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of-4-is 449:34.8:114, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-that weight ratio is 104:298:11.9, water, concentrated hydrochloric acid are added in the there-necked flask of 1L, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be 1:73:0.7, hydrogen is passed under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, add 100ml water recrystallization, ice bath filters after cooling down 1 hour, and filter cake is placed in vacuum drying oven at 80 DEG C dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
Embodiment 6
(S) preparation method of-3-hydroxyl tetrahydrofuran, its step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF that weight ratio is 90:85:65:356 are added in the there-necked flask of 1L, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in the four-hole bottle of 1L, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, oxolane, sodium borohydride, (S) weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of-4-is 450:35:115, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-that weight ratio is 105:300:12, water, concentrated hydrochloric acid are added in the there-necked flask of 1L, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be 0.9:72:0.8, hydrogen is passed under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, add 100ml water recrystallization, ice bath filters after cooling down 1 hour, and filter cake is placed in vacuum drying oven at 80 DEG C dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
The yield of embodiment 1-6 and comparative example is as shown in the table, and wherein, comparative example is publication number is the Chinese patent of CN104710357A:
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Comparative example | |
| Productivity/% | 79.6 | 78.6 | 78.8 | 79.4 | 80.3 | 79.5 | 73.2 |
As can be seen here, the yield of embodiment of the present invention 1-6 is above comparative example.
Above-described embodiment is illustrative principles of the invention and effect thereof only, not for the restriction present invention. Above-described embodiment all under the spirit and category of the present invention, can be modified or change by any those skilled in the art. Therefore, art has usually intellectual such as modifying without departing from all equivalences completed under disclosed spirit and technological thought or change, must be contained by the claim of the present invention.
Claims (9)
1. the preparation method of (S)-3-hydroxyl tetrahydrofuran, it is characterised in that step is as follows:
(1) (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF are added in there-necked flask, it is stirred at reflux 5 hours, remove DMF under reduced pressure, dry after washing with frozen water after standing 1 day, add 300ml dehydrated alcohol recrystallization, obtain the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-;
(2) by oxolane, sodium borohydride adds in four-hole bottle, this four-hole bottle is provided with agitator, thermometer and condensation reflux unit, stir 25 minutes at 45 DEG C, the chloro-3-benzyloxy ethyl n-butyrate. of (S)-4-is dripped under heat-retaining condition, stirring 5 hours is continued after dropwising, concentrated by rotary evaporation removes oxolane, 100ml concentrated hydrochloric acid and 250ml water is added after being cooled to 0 DEG C, being neutralized to ph value with sodium hydrate aqueous solution after stirring 1 hour is 7, use 500ml extraction into ethyl acetate, rectification after concentrated by rotary evaporation removal ethyl acetate, obtain the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-,
(3) chloro-for (S)-4-3-benzyloxy-n-butyl alcohol, water, concentrated hydrochloric acid are added in there-necked flask, open stirring, heat after 90 DEG C insulation reaction 15 hours, being neutralized to ph value with sodium hydrate aqueous solution is 7, use 500ml extraction into ethyl acetate, concentrated by rotary evaporation is distilled after removing ethyl acetate, obtains (S)-3-benzyloxy oxolane;
(4) (S)-3-benzyloxy oxolane is dissolved in oxolane, add the palladium carbon that mass fraction is 10%, passing into hydrogen under normal temperature and pressure conditions, maintenance Hydrogen Vapor Pressure is 0.1MPa, stirring reaction 12 hours under room temperature, filter and remove palladium carbon, concentrating under reduced pressure removes oxolane, adds 100ml water recrystallization, and ice bath filters after cooling down 1 hour, filter cake is placed in vacuum drying oven dry 20 hours, obtains (S)-3-hydroxyl tetrahydrofuran.
2. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterized in that: in described step (1), the weight ratio of (S)-4-chloro-3-hydroxyl ethyl n-butyrate., potassium carbonate, benzyl chloride and DMF is (85-90): (80-85): (60-65): (350-356).
3. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterised in that: in described step (1), the capacity of there-necked flask is 1L.
4. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterized in that: in described step (2), the weight ratio of the chloro-3-benzyloxy ethyl n-butyrate. of oxolane, sodium borohydride, (S)-4-is (444-450): (34-35): (110-115).
5. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterised in that: in described step (2), the capacity of four-hole bottle is 1L.
6. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterized in that: in described step (3), the chloro-3-benzyloxy-n-butyl alcohol of (S)-4-, water, concentrated hydrochloric acid weight ratio be (100-105): (290-300): (11.5-12).
7. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterised in that: in described step (3), the capacity of there-necked flask is 1L.
8. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterized in that: in described step (3), (S)-3-benzyloxy oxolane, oxolane, palladium carbon weight ratio be (0.9-1): (72-73): (0.6-0.8).
9. the preparation method of one according to claim 1 (S)-3-hydroxyl tetrahydrofuran, it is characterised in that: in described step (4), the baking temperature of vacuum drying oven is 80 DEG C.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107253939A (en) * | 2017-06-23 | 2017-10-17 | 郑州泰基鸿诺医药股份有限公司 | The preparation method of 3 benzyloxy oxinanes and preparation method thereof, the cyclic alcohol of oxinane 3 of single configuration |
| CN107935971A (en) * | 2017-12-28 | 2018-04-20 | 山东铂源药业有限公司 | It is a kind of（S）The preparation method of 3 hydroxyl tetrahydrofurans |
| CN115611829A (en) * | 2021-07-13 | 2023-01-17 | 中化医药有限公司 | Preparation method of (S) -3-hydroxytetrahydrofuran |
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| WO2008093955A1 (en) * | 2007-02-01 | 2008-08-07 | Rstech Corporation | Process for the efficient preparation of 3-hydroxytetrahydrofuran |
| CN102477019A (en) * | 2010-11-26 | 2012-05-30 | 苏州凯达生物医药技术有限公司 | Novel method for producing S-3-hydroxytetrahydrofuran |
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| WO2008093955A1 (en) * | 2007-02-01 | 2008-08-07 | Rstech Corporation | Process for the efficient preparation of 3-hydroxytetrahydrofuran |
| CN102477019A (en) * | 2010-11-26 | 2012-05-30 | 苏州凯达生物医药技术有限公司 | Novel method for producing S-3-hydroxytetrahydrofuran |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107253939A (en) * | 2017-06-23 | 2017-10-17 | 郑州泰基鸿诺医药股份有限公司 | The preparation method of 3 benzyloxy oxinanes and preparation method thereof, the cyclic alcohol of oxinane 3 of single configuration |
| CN107253939B (en) * | 2017-06-23 | 2019-12-27 | 郑州泰基鸿诺医药股份有限公司 | 3-benzyloxy-tetrahydropyran, preparation method thereof and preparation method of tetrahydropyran-3-cyclic alcohol with single configuration |
| CN107935971A (en) * | 2017-12-28 | 2018-04-20 | 山东铂源药业有限公司 | It is a kind of（S）The preparation method of 3 hydroxyl tetrahydrofurans |
| CN107935971B (en) * | 2017-12-28 | 2020-04-14 | 山东铂源药业有限公司 | Preparation method of (S) -3-hydroxytetrahydrofuran |
| CN115611829A (en) * | 2021-07-13 | 2023-01-17 | 中化医药有限公司 | Preparation method of (S) -3-hydroxytetrahydrofuran |
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