CN107162920B - A kind of preparation method of R-1- amino -2- propyl alcohol - Google Patents
A kind of preparation method of R-1- amino -2- propyl alcohol Download PDFInfo
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- CN107162920B CN107162920B CN201610128208.0A CN201610128208A CN107162920B CN 107162920 B CN107162920 B CN 107162920B CN 201610128208 A CN201610128208 A CN 201610128208A CN 107162920 B CN107162920 B CN 107162920B
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- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 150000002576 ketones Chemical class 0.000 claims abstract description 14
- GOOHAUXETOMSMM-GSVOUGTGSA-N R-propylene oxide Chemical compound C[C@@H]1CO1 GOOHAUXETOMSMM-GSVOUGTGSA-N 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 11
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 8
- 230000006837 decompression Effects 0.000 claims description 8
- 239000012043 crude product Substances 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical group COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims 2
- 238000005292 vacuum distillation Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 abstract description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 12
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract description 8
- 229910021529 ammonia Inorganic materials 0.000 abstract description 6
- 229960004556 tenofovir Drugs 0.000 abstract description 6
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 abstract description 6
- 230000007062 hydrolysis Effects 0.000 abstract description 5
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000004473 Threonine Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 229960002898 threonine Drugs 0.000 abstract description 4
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- -1 azido compound Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
- 229960001627 lamivudine Drugs 0.000 description 2
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 2
- 229910001948 sodium oxide Inorganic materials 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical class ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940013688 formic acid Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
Abstract
The present invention relates to field of medicaments, the specially preparation method of one kind (R) -1- amino -2- propyl alcohol.(R) -1- amino -2- propyl alcohol of high-optical-purity is prepared using one kettle way using (R)-propylene oxide as raw material, which is a kind of original production new technique for utilizing L-threonine also original production (R) -1- amino -2- propyl alcohol of substitution.(R) -1- amino -2- propyl alcohol is the important intermediate prepared such as anti-AIDS drugs tenofovir, and (R)-propylene oxide, ammonia and ketone are added in reaction kettle by the present invention to react, obtained intermediate hydrolysis, concentration, rectification and purification.It is thus possible to solve the problems, such as that cost of material is high, yield is low, tenofovir increased costs.The present invention is substantially reduced production cost, and no waste generates, and without environmental pollution, realizes green production, and raw material is cheap and easy to get, and step is simply at low cost, and product purity is high, is suitble to industrialized production.
Description
Technical field
The present invention relates to field of medicaments, the specially preparation method of one kind (R) -1- amino -2- propyl alcohol.
Background technique
(R) -1- amino -2- propyl alcohol is widely used in preparation medicine and pesticide, hand as a kind of important synthetic intermediate
Property compound (R) -1- amino -2- propyl alcohol is the important intermediate of the synthesis of nucleoside drug (such as: anti-AIDS drugs tenofovir).
Tenofovir is the nucleotide reverse transcriptase inhibitors of GileadSciences company, U.S. research and development, is the prodrug of tenofovir,
U.S.'s listing for the first time in 2001, clinic are mainly used for treating human immunodeficiency virus (HIV) infection, and can be degeneration-resistant with other
Retroviral agent combination, but also have good anti-hepatitis B virus (HBV) activity, to merge HIV/HBV infection and
Lamivudine (lamivudine) persister is effective.
Currently, the method for synthesis R-1- amino -2- propyl alcohol is broadly divided into following three kinds both at home and abroad:
It one, is produced under the action of 2- cyclohexene -1- ketone in polyglycol solution high temperature decarboxylation by L-threonine
Product (US2005222430, US2014275569), L-threonine is cheap, but 2- cyclohexene -1- ketone is expensive, and
And 160 degree of high temperature are needed, industrialization degree is low；
Two, propylene oxide reacts under chiral catalyst CSA effect with cyano trimethyl silane, is then restored using Pd/c
Obtain product (Journal of the American Chemical Society；vol.118；nb.31；(1996)；
P.7420-7421), this synthetic method cost of material is high, and intermediate azido compound risk is high, hardly possible purification；
Three, (JP 2011079782) is split using the derivative of tartaric acid, resolution yield is low, and ee value can only
Reach 98%.
Summary of the invention
(R) -1- amino -2- propyl alcohol synthesis material risk is big, investment of production is big in order to solve in the prior art, and product is not
The deficiency being easily purified, (R) -1- amino -2- propyl alcohol that the present invention provides a kind of raw materials to be easy to get, at low cost, product is easily purified
Preparation method.
The technical scheme is that
A kind of preparation method of R-1- amino -2- propyl alcohol, according to parts by weight, room temperature is by 100~400 parts of ketone and 0.5~2
Part catalyst is added in there-necked flask, is passed through 30~40 parts of ammonias and is stirred 2~12h；55~65 parts of chiral epoxy propane are added dropwise
Into reaction flask, drop finishes, and is heated to reflux, and reacts 2~12h；Cooling decompression distills excessive ketone, obtain crude product directly add 500~
1000 parts of hydrochloric acid hydrolysis, are stirred at room temperature 0.5~6h, and adding sodium hydroxide aqueous solution tune pH=9~11 are evaporated under reduced pressure filtrate, rectifying
Obtain product；
The synthetic route of R-1- amino -2- propyl alcohol is as follows:
A kind of preparation method of R-1- amino -2- propyl alcohol, according to parts by weight, room temperature is by 100~400 parts of ketone and 0.5~2
Part catalyst is added in there-necked flask, is passed through 30~40 parts of ammonias and is stirred 2~12h；55~65 parts of chiral epoxy propane are added dropwise
Into reaction flask, drop finishes, and is heated to reflux, and reacts 2~12h；Cooling decompression distills excessive ketone, obtain crude product directly add 500~
1000 parts of hydrochloric acid hydrolysis, are stirred at room temperature 0.5~6h, and adding sodium hydroxide aqueous solution tune pH=9~11 are evaporated under reduced pressure filtrate, through essence
Evaporate to obtain product；
The synthetic route of R-1- amino -2- propyl alcohol is as follows:
Wherein, R1=R2=methyl, ethyl, propyl, phenyl or naphthyl；Alternatively, R1=methyl, R2=ethyl, propyl, fourth
Base；Alternatively, R1=ethyl, R2=propyl, butyl.
The preparation method of the R-1- amino -2- propyl alcohol, catalyst are formic acid, acetic acid, methanesulfonic acid, oxalic acid, three chloroethenes
Acid or trifluoroacetic acid.
The preparation method of the R-1- amino -2- propyl alcohol, concentration of hydrochloric acid are 4~36wt%.
The preparation method of the R-1- amino -2- propyl alcohol, the concentration of sodium hydrate aqueous solution are 5~50wt%.
The preparation method of the R-1- amino -2- propyl alcohol, chiral epoxy propane are (R)-(+) -1,2- propylene oxide.
The preparation method of the R-1- amino -2- propyl alcohol, ketone are cyclohexanone, alkyl ketone, acetone or butanone.
The invention has the advantages and beneficial effects that:
1, the present invention prepares (the R) -1- amino -2 third of high-optical-purity using (R)-propylene oxide as raw material using one kettle way
Alcohol, the production technology are a kind of original production new techniques for utilizing L-threonine also original production (R) -1- amino -2- propyl alcohol of substitution.
(R) -1- amino -2- propyl alcohol is the important intermediate prepared such as anti-AIDS drugs tenofovir, the present invention by (R)-propylene oxide,
Ammonia and ketone, which are added in reaction kettle, to react, obtained intermediate hydrolysis, concentration, rectification and purification.
2, the present invention is substantially reduced production cost, and no waste generates, and without environmental pollution, realizes green production, raw material
Cheap and easy to get, step is simply at low cost, and product purity is high, is suitble to industrialized production.
Detailed description of the invention
Fig. 1 is compound in embodiment 11H NMR figure.
Fig. 2 a- Fig. 2 b is that compound GC schemes (Fig. 2 a) and analysis result table (Fig. 2 b) in embodiment 1.
Fig. 3 is to scheme outside compound of red in embodiment 1；Wherein, abscissa wavenumber is wave number (cm-1), ordinate
Transmittance is transmitance (%).
Specific embodiment
In the specific implementation process, the preparation method of the present invention (R) -1- amino -2- propyl alcohol, includes the following steps:
Ketone, ammonia and a small amount of catalyst are added in reaction flask, heat temperature raising, react 2~12h, chiral epoxy is added dropwise
Propane, reacts 2~12h, and cooling decompression distills out excessive ketone.Then the acid (N is equivalent concentration) of 1N~12N, stirring 0.5 is added
Then~6h utilizes sodium hydroxide tune pH=9~11, be evaporated under reduced pressure filtrate using water pump, by the production of rectifying preparation high-purity
Product, content are greater than 99wt%.
In the following, by embodiment, the present invention is described in more detail.
Embodiment 1
The synthetic route of the present embodiment (R) -1- amino -2- propyl alcohol is as follows:
Wherein, R1=R2=methyl, ethyl, propyl, phenyl or naphthyl.
290g acetone and 1g glacial acetic acid are added in there-necked flask by room temperature, 35g ammonia stirring 4h are passed through, by 58g (R)-
(+) -1,2- propylene oxide are added drop-wise in reaction flask, and drop finishes, and are heated to reflux, and 2h is reacted, and cooling decompression distills excessive propanone, obtains
Crude product directly adds 800g dilute hydrochloric acid (dilute hydrochloric acid concentration is 5wt%) hydrolysis, and 30min, adding sodium hydroxide aqueous solution (hydrogen is stirred at room temperature
The concentration of aqueous solution of sodium oxide is 10wt%) pH=10 is adjusted, it is evaporated under reduced pressure filtrate, obtains product 56g, yield 74.66% through rectifying.
It is detected through gas chromatography, content > 99wt% of (R) -1- amino -2- propyl alcohol.
As shown in Figure 1, the pedigree of the present embodiment (R) -1- amino -2- propyl alcohol nuclear magnetic resonance is as follows: 1H NMR (400MHz,
DMSO-d6): δ 3.44-3.47 (m, 1H), 2.39-2.42 (dd, 1H), 2.33-2.36 (dd, 1H), 0.97-0.98 (d, 1H),
These data illustrate that (R) -1- amino -2- propyl alcohol structure made from the present embodiment is correct.
As shown in Fig. 2 a- Fig. 2 b, the present embodiment (R) -1- amino -2- propyl alcohol gas phase spectrogram is as follows: RT=3.316, (R) -
The content of 1- amino -2- propyl alcohol: 99.99wt%.
As shown in figure 3, scheming according to outside compound of red it can be seen that IR (cm-1): 3360 (vs), 3298 (vs), 2966
(vs),2928(vs),2867(vs),1597(s),1458(s),1374(s),1334(m),1190(m),1137(s),1064
(s),968(s),919(s),821(m),512(w)),481(w)。
Embodiment 2
The synthetic route of the present embodiment (R) -1- amino -2- propyl alcohol is as follows:
Wherein, R1=methyl, R2=ethyl, propyl, butyl；Alternatively, R1=ethyl, R2=propyl, butyl.
360g butanone and 1g glacial acetic acid are added in there-necked flask by room temperature, 35g ammonia stirring 4h are passed through, by 58g (R)-
(+) -1,2- propylene oxide are added drop-wise in reaction flask, and drop finishes, and are heated to reflux, and 2h is reacted, and cooling decompression distills excessive butanone, obtains
Crude product directly adds 800g dilute hydrochloric acid (dilute hydrochloric acid concentration is 5wt%) hydrolysis, and 30min, adding sodium hydroxide aqueous solution (hydrogen is stirred at room temperature
The concentration of aqueous solution of sodium oxide is 10wt%) pH=10 is adjusted, it is evaporated under reduced pressure filtrate, obtains product 52.12g, yield through rectifying
69.49%.It is detected through gas chromatography, content > 99wt% of (R) -1- amino -2- propyl alcohol.
Embodiment 3
The synthetic route of the present embodiment (R) -1- amino -2- propyl alcohol is as follows:
294g cyclohexanone and 1g glacial acetic acid are added in there-necked flask by room temperature, 35g ammonia stirring 4h are passed through, by 58g (R)-
(+) -1,2- propylene oxide are added drop-wise in reaction flask, and drop finishes, and are heated to reflux, and 2h is reacted, and cooling decompression distills excessive cyclohexanone, obtains
Directly add 800g dilute hydrochloric acid (dilute hydrochloric acid concentration is 5wt%) hydrolysis to crude product, 30min, adding sodium hydroxide aqueous solution is stirred at room temperature
(concentration of sodium hydrate aqueous solution is 10wt%) adjusts pH=10, is evaporated under reduced pressure filtrate, rectifying obtains product 61.28g, yield
81.70%.It is detected through gas chromatography, content > 99wt% of (R) -1- amino -2- propyl alcohol.
Claims (5)
1. a kind of preparation method of R-1- amino -2- propyl alcohol, which is characterized in that according to parts by weight, room temperature is by 100~400 parts
Ketone and 0.5~2 part of catalyst are added in there-necked flask, are passed through 30~40 parts of ammonias and are stirred 2~12h；By 55~65 parts of chiral rings
Ethylene Oxide is added drop-wise in reaction flask, and drop finishes, and is heated to reflux, and 2~12h is reacted；Cooling decompression distills excessive ketone, and it is direct to obtain crude product
Add 500~1000 parts of hydrochloric acid hydrolysis, 0.5~6h, adding sodium hydroxide aqueous solution tune pH=9~11, vacuum distillation filter is stirred at room temperature
Liquid, rectifying obtain product；
The synthetic route of R-1- amino -2- propyl alcohol is as follows:
Catalyst is formic acid, acetic acid, methanesulfonic acid, oxalic acid, trichloroacetic acid or trifluoroacetic acid, and chiral epoxy propane is (R)-(+) -1,
2- propylene oxide.
2. a kind of preparation method of R-1- amino -2- propyl alcohol, which is characterized in that according to parts by weight, room temperature is by 100~400 parts
Ketone and 0.5~2 part of catalyst are added in there-necked flask, are passed through 30~40 parts of ammonias and are stirred 2~12h；By 55~65 parts of chiral rings
Ethylene Oxide is added drop-wise in reaction flask, and drop finishes, and is heated to reflux, and 2~12h is reacted；Cooling decompression distills excessive ketone, and it is direct to obtain crude product
Add 500~1000 parts of hydrochloric acid hydrolysis, 0.5~6h, adding sodium hydroxide aqueous solution tune pH=9~11, vacuum distillation filter is stirred at room temperature
Liquid obtains product through rectifying；
The synthetic route of R-1- amino -2- propyl alcohol is as follows:
Wherein, R1=R2=methyl, ethyl, propyl, phenyl or naphthyl；Alternatively, R1=methyl, R2=ethyl, propyl, butyl；
Alternatively, R1=ethyl, R2=propyl, butyl；
Catalyst is formic acid, acetic acid, methanesulfonic acid, oxalic acid, trichloroacetic acid or trifluoroacetic acid, and chiral epoxy propane is (R)-(+) -1,
2- propylene oxide.
3. the preparation method of R-1- amino -2- propyl alcohol according to claim 1 or 2, which is characterized in that concentration of hydrochloric acid 4
~36wt%.
4. the preparation method of R-1- amino -2- propyl alcohol according to claim 1 or 2, which is characterized in that sodium hydroxide is water-soluble
The concentration of liquid is 5~50wt%.
5. the preparation method of R-1- amino -2- propyl alcohol according to claim 1 or 2, which is characterized in that ketone be cyclohexanone,
Acetone or butanone.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020069814A (en) * | 2001-02-28 | 2002-09-05 | 에스케이 주식회사 | Mothod for preparing (R)-1-amino-2-propanol using hydrolysis enzyme |
| CN1887855A (en) * | 2006-07-18 | 2007-01-03 | 上海科利生物医药有限公司 | Prepn of (S)-(+)-2-amino propanol |
| WO2012159992A1 (en) * | 2011-05-20 | 2012-11-29 | Interquim, S.A. | Process for obtaining rivaroxaban and intermediate thereof |
| CN103664673A (en) * | 2013-12-18 | 2014-03-26 | 成都医路康医学技术服务有限公司 | Preparation method of linezolid side chain |
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2016
- 2016-03-08 CN CN201610128208.0A patent/CN107162920B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020069814A (en) * | 2001-02-28 | 2002-09-05 | 에스케이 주식회사 | Mothod for preparing (R)-1-amino-2-propanol using hydrolysis enzyme |
| CN1887855A (en) * | 2006-07-18 | 2007-01-03 | 上海科利生物医药有限公司 | Prepn of (S)-(+)-2-amino propanol |
| WO2012159992A1 (en) * | 2011-05-20 | 2012-11-29 | Interquim, S.A. | Process for obtaining rivaroxaban and intermediate thereof |
| CN103664673A (en) * | 2013-12-18 | 2014-03-26 | 成都医路康医学技术服务有限公司 | Preparation method of linezolid side chain |
Non-Patent Citations (1)
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| An Effective Method To Prepare Imines from Aldehyde,Bromide/Epoxide, and Aqueous Ammonia;Jing-Mei Huang等;《J. Org. Chem.》;20111231;第76卷;第3511-3514页 |
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