CN116675593A - Method for selectively removing hydroxyl protecting group - Google Patents

Method for selectively removing hydroxyl protecting group Download PDF

Info

Publication number
CN116675593A
CN116675593A CN202310640948.2A CN202310640948A CN116675593A CN 116675593 A CN116675593 A CN 116675593A CN 202310640948 A CN202310640948 A CN 202310640948A CN 116675593 A CN116675593 A CN 116675593A
Authority
CN
China
Prior art keywords
selectively removing
hydroxyl protecting
chloroacetate
protecting groups
potassium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202310640948.2A
Other languages
Chinese (zh)
Inventor
张胜
李仁花
包明
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dalian University of Technology
Original Assignee
Dalian University of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dalian University of Technology filed Critical Dalian University of Technology
Priority to CN202310640948.2A priority Critical patent/CN116675593A/en
Publication of CN116675593A publication Critical patent/CN116675593A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
    • C07C29/095—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of esters of organic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
    • C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
    • C07C37/0555—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group being esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/29—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
    • C07H9/02—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
    • C07H9/04—Cyclic acetals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention belongs to the technical field of fine chemicals and related chemistry, and provides a method for selectively removing hydroxyl protecting groups. The method is characterized in that chloroacetate and derivatives thereof are used as raw materials, under the existence of a phosphine catalyst and the existence of alkali and additives, the corresponding deprotected compound can be obtained after the reaction for 1 to 16 hours at 80 ℃ under the condition of anhydrous organic solvent. The method has the advantages of no transition metal, mild reaction conditions, simple and convenient operation, possibility of realizing industrialization and higher yield of the deprotected compound; the deprotected compound obtained by the method can be further functionalized to obtain various compounds, and the method is applied to development and research of natural products, functional materials and fine chemicals.

Description

Method for selectively removing hydroxyl protecting group
Technical Field
The invention belongs to the technical field of fine chemicals and related chemistry, and provides a method for efficiently and selectively removing a hydroxyl protecting group chloroacetyl group.
Background
Hydroxy compounds are a class of hydroxyl (-OH) -containing organic molecules that are widely found in natural products and in some important and complex compounds. It is well known that hydroxyl groups are active in chemical reactivity, and therefore, protection and deprotection of hydroxyl groups are often involved in hydroxyl-containing natural products and pharmaceutical syntheses, and therefore, it is important to select suitable protecting groups and develop corresponding deprotection methods. Compared with other protecting groups, the chloracetyl has the characteristics of simple introduction and relatively easy removal.
Among the methods reported for removing the chloroacetyl protecting group are thiourea (M Bertolini, C.P.J.Glaudemans, carbohyd.Rea.1970,15, 263-270), HDTC (C.A.A.van Boeckel and T.Beetz, tetrahedron Lett.1983,24, 3775-3778), DABCO (I.Ohtsuka, T.Ako, R.Kato, S.Daikoku, S.Koroghi, T.Kanemitsu, O.Kanie, carbohyd.Res.2006,341,1476-1487), piperidine 1-Se-substituted carbamate (S.Sogabe, H.Ando, M.Koketsub, H.Ishihara, tetrahedron Lett.2006,47, 6603-6606) which has been a good choice, and the use of NaBH has been proposed in recent years 4 (E.Villedieu, C.L.Bon, S.B.Raboin, tetrahedron letters 2010,51, 2115-2118) to remove chloroacetyl groups.
However, these methods have their own drawbacks, such as thiourea facilitating cleavage of the ClAc group, requiring relatively harsh reaction conditions and long reaction times, and occasionally causing acyl migration. HDTC has poor chemical stability and needs to be used immediately after fresh formulation. The use of DABCO is limited to the reaction medium being limited to ethanol solvents only. The recently reported 1-Se carbamic acid piperidine shows higher chemical selectivity and wide tolerance to reaction solvents in dechlorination and acetylation reaction, but is also limited by complicated preparation of selenourea intermediates and high reaction temperature. The reducing ability of sodium borohydride causes problems with functional group compatibility.
In recent years, reactions without metal catalysis are becoming better appreciated by more and more people, because of the advantages of small pollution, low price, capability of being put into industrial production and the like. The method for removing the chloroacetyl by taking the phosphine compound as a catalyst is not reported at present.
Disclosure of Invention
The invention provides a method for selectively removing hydroxyl protecting group chloroacetyl, which has the advantages of no transition metal existence, mild reaction condition, simple operation, high efficiency and high yield.
The technical scheme of the invention is as follows:
a method for selectively removing hydroxyl protecting group (AcCl) takes chloracetyl ester compound and its derivative as raw material, in the presence of phosphine catalyst, in the presence of alkali and additive, under the condition of anhydrous organic solvent, reacting for 1-16 hours at 80 ℃ to obtain corresponding deprotected product alcohol, the synthetic route is as follows:
R 1 selected from aryl and alkyl;
the molar ratio of the chloroacetate and the derivative thereof to the phosphine catalyst is 1:0.01-1:0.1;
the molar ratio of the chloroacetate and the derivative thereof to the alkali is 1:0.5-1:3;
the molar ratio of the chloroacetate to the derivatives and the additives is 1:0.5-1:3;
the molar concentration of chloroacetate and its derivatives in the reaction system was 0.3mmol/mL.
The anhydrous organic solvent is toluene, acetonitrile, 1, 4-dioxane or tetrahydrofuran. Toluene, acetonitrile, 1, 4-dioxane are preferred.
The phosphine catalyst is triphenylphosphine, DPPF, tri-n-butylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine, or tri (2-furyl) phosphine. Preferably tris (2-furyl) phosphine, triphenylphosphine, DPPF;
the alkali is sodium tert-butoxide, potassium tert-butoxide, cesium carbonate, sodium hydroxide, potassium hydroxide, cesium fluoride, potassium carbonate, potassium acetate, potassium phosphate and potassium pyrophosphate. Preferably potassium phosphate, sodium hydroxide, potassium hydroxide.
The additive is triisobutyl borate, triethyl borate, trimethyl borate and boric acid. Preferred are trimethyl borate, triethyl borate, triisobutyl borate.
The separation method comprises recrystallization, column chromatography and the like.
Solvents used in the recrystallization method include petroleum ether, ethyl acetate, diethyl ether, acetone, chloroform, n-hexane and dichloromethane.
When the product is separated by column chromatography, silica gel or neutral alumina can be used as stationary phase, and the developing agent is generally mixed solvent of polarity and nonpolar, such as ethyl acetate-petroleum ether, ethyl acetate-n-hexane, dichloromethane-petroleum ether, and methanol-petroleum ether.
The invention has the advantages that the synthesis method has no transition metal reaction, mild reaction conditions, simple and convenient operation and high yield; the hydroxy compound obtained by deprotection by the method can be further functionalized to obtain various compounds, and is applied to development and research of natural products, functional materials and fine chemicals.
Drawings
FIG. 1 is benzyl alcohol of example 1 1 H nuclear magnetic spectrum.
FIG. 2 is benzyl alcohol of example 1 13 C nuclear magnetic spectrogram.
FIG. 3 is 2-allylphenol in example 2 1 H nuclear magnetic spectrum.
FIG. 4 is a 2-alkene of example 2Propylphenol 13 C nuclear magnetic spectrogram.
FIG. 5 is beta-cholesterol in example 3 1 H nuclear magnetic spectrum.
FIG. 6 is beta-cholesterol in example 3 13 C nuclear magnetic spectrogram.
FIG. 7 is diacetone-D-galactose in example 4 1 H nuclear magnetic spectrum.
FIG. 8 is diacetone-D-galactose in example 4 13 C nuclear magnetic spectrogram.
FIG. 9 is 1-adamantanol of example 5 1 H nuclear magnetic spectrum.
FIG. 10 is 1-adamantanol of example 5 13 C nuclear magnetic spectrogram.
FIG. 11 is (S) - (-) -ethyl mandelate of example 6 1 H nuclear magnetic spectrum.
FIG. 12 is (S) - (-) -ethyl mandelate of example 6 13 C nuclear magnetic spectrogram.
FIG. 13 is benzyl 3- (hydroxymethyl) benzoate in example 7 1 H nuclear magnetic spectrum.
FIG. 14 is benzyl 3- (hydroxymethyl) benzoate in example 7 13 C nuclear magnetic spectrogram.
FIG. 15 is (-) - (1 r,3r,4s,8 r) -menthane-3, 9-diol of example 8 1 H nuclear magnetic spectrum.
FIG. 16 is (-) - (1 r,3r,4s,8 r) -menthane-3, 9-diol of example 8 13 C nuclear magnetic spectrogram.
Detailed Description
The synthesis method for removing the hydroxyl protecting group has the advantages of low raw material cost, no participation of transition metal in the reaction, few reaction steps, mild reaction conditions, convenient operation, high reaction yield and the like.
The invention will be further illustrated with reference to specific examples. These examples are only for illustrating the present invention and are not intended to limit the scope of the present invention. Simple alternatives and modifications of the invention by those skilled in the art are within the scope of the invention as claimed.
Example 1: synthesis of benzyl alcohol
To a 25mL reactor was added benzyl chloroacetate (0.055 g,0.3 mmol), potassium phosphate (0.191 g,0.9 mmol), triphenylphosphine (0.78 mg, 0.003mmol), trimethyl borate (0.046 g,0.45 mmol), and 1.5mL of anhydrous acetonitrile was added and stirred under nitrogen for 1h. Column chromatography (silica gel, 200-300 mesh; developing solvent, petroleum ether: dichloromethane=1:2) gave benzyl alcohol 0.030g, 94% yield.
Benzyl alcohol, a colorless oily liquid, 1 H NMR(400MHz,CDCl 3 )δ7.33(d,J＝6.1Hz,4H),7.30–7.24(m,1H),4.62(s,2H),2.32(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ140.9,128.6,127.6,127.0,65.2.
example 2: synthesis of 2-allylphenol
In a 25mL reactor, 2-allylphenyl 2-chloroacetate (0.063 g,0.3 mmol), potassium phosphate (0.191 g,0.9 mmol), tris (2-furyl) phosphine (0.1 mg, 0.003mmol), triethyl borate (0.065 g,0.45 mmol) was added, and anhydrous acetonitrile 1.5mL was added and stirred under nitrogen for 4h at 80 ℃. Column chromatography (silica gel, 200-300 mesh; developing solvent, petroleum ether: dichloromethane=1:2) gave 0.039g of 2-allylphenol in 97% yield.
2-allylphenol, colorless liquid, 1 H NMR(400MHz,CDCl3)δ7.18–7.07(m,2H),6.91–6.87(m,J＝7.5,1.2Hz,1H),6.82–8.80(dd,J＝7.9,1.1Hz,1H),6.07-5.97(m,J＝17.9,9.6,6.3Hz,1H),5.20–5.11(m,2H),5.00(s,1H),3.41(dt,J＝6.4,1.7Hz,2H)； 13 C NMR(101MHz,CDCl3)δ154.1,136.4,130.5,127.9,125.3,121.0,116.5,115.8,35.1.
example 3: synthesis of beta-cholesterol
The procedure of example 1 was followed to give β -cholesterol from cholesterol chloroacetate, 0.060g, 52% yield.
Beta-cholesterol, a pale yellow solid, 1 H NMR(400MHz,CDCl 3 )δ5.35(s,1H),3.52(tt,J＝10.6,4.7Hz,1H),2.35–2.16(m,2H),1.99(tt,J＝16.3,3.1Hz,2H),1.84(dq,J＝14.4,5.1,4.3Hz,3H),1.73(s,1H),1.62–0.94(m,24H),0.91(d,J＝6.5Hz,3H),0.86(dd,J＝6.6,1.8Hz,6H),0.68(s,3H)； 13 C NMR(101MHz,CDCl 3 )δ140.8,121.7,71.8,56.8,56.2,50.1,42.33,42.30,39.8,39.5,37.3,36.5,36.2,35.8,31.93,31.91,31.7,28.3,28.0,24.3,23.9,22.9,22.6,21.1,19.4,18.7,11.9.
example 4: synthesis of diacetone-D-galactose
The procedure of example 2 was followed, giving diacetone-D-galactose from diacetone-D-galactose chloroacetate 0.048g in 64% yield.
diacetone-D-galactose, colorless oily liquid, 1 H NMR(400MHz,CDCl 3 )δ5.94(d,J＝3.6Hz,1H),4.53(d,J＝3.6Hz,1H),4.39–4.26(m,2H),4.17(dd,J＝8.7,6.4Hz,1H),4.06(dd,J＝7.9,2.6Hz,1H),4.00(dd,J＝8.7,5.3Hz,1H),2.82(d,J＝3.9Hz,1H),1.47(d,J＝21.5Hz,6H),1.34(d,J＝19.1Hz,6H)； 13 C NMR(101MHz,CDCl 3 )δ111.8,109.6,105.3,85.1,81.1,75.0,73.3,67.6,26.84,26.78,26.2,25.2.
example 5: synthesis of 1-adamantanol
Into a 25mL reactor was added adamantyl chloroacetate (0.067 g,0.3 mmol), sodium hydroxide (0.036 g,0.9 mmol), DPPF (0.002 g, 0.003mmol), triisobutyl borate (0.103 g,0.45 mmol), and 1.5mL of anhydrous toluene was added and stirred under nitrogen for 16h. Column chromatography (silica gel, 200-300 mesh; developing solvent, petroleum ether: dichloromethane=1:2) gave 0.033g of 1-adamantanol, 73% yield.
1-adamantanol, white solid, 1 H NMR(400MHz,CDCl 3 )δ4.94(s,1H),3.97(s,1H),2.13(t,J＝3.0Hz,4H),1.71(d,J＝3.0Hz,4H),1.66(d,J＝3.4Hz,2H),1.64–1.59(m,4H)； 13 C NMR(101MHz,CDCl 3 )δ68.2,45.3,36.1,30.7.
example 6: synthesis of (S) - (-) -ethyl mandelate
The same procedures used in example 5 were repeated except for using ethyl (S) -2- (2-chloroacetoxy) -2-phenylacetate to give ethyl mandelate in an yield of 0.045g and 86%.
Ethyl mandelate, colorless liquid, 1 H NMR(400MHz,CDCl 3 )δ7.47–7.39(m,2H),7.39–7.27(m,3H),5.15(d,J＝5.8Hz,1H),4.30–4.10(m,2H),3.56(d,J＝5.8Hz,1H),1.22(t,J＝7.1Hz,3H)； 13 C NMR(101MHz,CDCl 3 )δ173.7,138.5,128.6,128.4,126.6,72.9,62.2,14.0.
example 7: synthesis of benzyl 3- (hydroxymethyl) benzoate
The same procedures used in example 5 were repeated except for using benzyl 3- ((2-chloroacetoxy) methyl) benzoate to give 0.057g of 2-allylphenol in 79% yield.
Benzyl 3- (hydroxymethyl) benzoate, a pale yellow liquid, 1 H NMR(400MHz,CDCl 3 )δ8.12–8.04(m,2H),7.60–7.46(m,J＝7.4Hz,1H),7.49–7.41(m,3H),7.43–7.31(m,3H),5.37(s,2H),4.72(s,2H),2.25(s,1H)； 13 C NMR(101MHz,CDCl 3 )δ166.5,141.4,136.4,133.1,130.1,129.7,128.9,128.4,127.4,126.9,126.7,66.6,65.0；IR(neat)3337,1718,1451,1273,1112,1026,887,788,744,711cm -1 ；HMRS(ESI)calcd for C 15 H 14 NaO 3 265.0841[M+Na] + ,found 265.0831.
example 8: synthesis of (-) - (1 r,3r,4s,8 r) -menthane-3, 9-diol
In a 25mL reactor, (1R, 2S, 5R) -2- (((R) -1-hydroxypropyl-2-yl) -5-methylcyclohexyl-2-chloroacetate (0.074 g,0.3 mmol), potassium hydroxide (0.050 g,0.9 mmol.), DPPF (0.002 g, 0.003mmol), triisobutyl borate (0.103 g,0.45 mmol) were added, anhydrous 1, 4-dioxane (1.5 mL,80 ℃ C.) and stirred under nitrogen for 1h column chromatography (silica gel, 200-300 mesh; developer, petroleum ether: dichloromethane=1:2) to give (-) - (1R, 3R,4s, 8R) -menthane-3, 9-diol, 0.048g, 93% yield.
(-) - (1 r,3r,4s,8 r) -menthane-3, 9-diol, colorless liquid, 1 H NMR(400MHz,CDCl 3 )δ4.09(s,1H),3.64(dd,J＝10.7,5.3Hz,1H),3.56(dd,J＝10.7,3.4Hz,1H),3.43(td,J＝10.4,4.3Hz,1H),1.98(d,J＝4.4Hz,1H),1.82(s,1H),1.69–1.50(m,2H),1.47–1.29(m,2H),1.23(qd,J＝12.7,3.4Hz,1H),0.99(d,J＝11.6Hz,1H),0.95(d,J＝7.2 Hz,3H),0.92(d,J＝6.6 Hz,3H),0.88–0.81(m,1H)； 13 C NMR(101 MHz,CDCl 3 )δ69.9,66.9,48.6,44.4,38.6,34.6,31.4,29.6,22.1,12.0。

Claims (5)

1. a method for selectively removing hydroxyl protecting groups is characterized in that a chloracetyl ester compound and derivatives thereof are used as raw materials, under the existence of a phosphine catalyst and the existence of alkali and additives, the raw materials react for 1 to 16 hours at 80 ℃ under the condition of anhydrous organic solvent, and the corresponding deprotected product alcohol is obtained, wherein the synthetic route is as follows:
the molar ratio of the chloroacetate and the derivative thereof to the phosphine catalyst is 1:0.01-1:0.1;
the molar ratio of the chloroacetate and the derivative thereof to the alkali is 1:0.5-1:3;
the molar ratio of the chloroacetate to the derivatives and the additives is 1:0.5-1:3;
the molar concentration of chloroacetate and its derivatives in the reaction system was 0.3mmol/mL.
2. The method for selectively removing hydroxyl protecting groups according to claim 1, wherein the anhydrous organic solvent is one or more of toluene, acetonitrile, 1, 4-dioxane and tetrahydrofuran.
3. The method for selectively removing hydroxyl protecting groups according to claim 1, wherein the phosphine catalyst is one or a mixture of more than two of triphenylphosphine, DPPF, tri-n-butylphosphine, tricyclohexylphosphine, tri-tert-butylphosphine and tri (2-furyl) phosphine.
4. The method for selectively removing hydroxyl protecting groups according to claim 1, wherein the base is one or more of sodium tert-butoxide, potassium tert-butoxide, cesium carbonate, sodium hydroxide, potassium hydroxide, cesium fluoride, potassium carbonate, potassium acetate, potassium phosphate, and potassium pyrophosphate.
5. The method for selectively removing hydroxyl protecting groups according to claim 1, wherein the additive is one or more of triisobutyl borate, triethyl borate, trimethyl borate and boric acid.
CN202310640948.2A 2023-06-01 2023-06-01 Method for selectively removing hydroxyl protecting group Pending CN116675593A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310640948.2A CN116675593A (en) 2023-06-01 2023-06-01 Method for selectively removing hydroxyl protecting group

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310640948.2A CN116675593A (en) 2023-06-01 2023-06-01 Method for selectively removing hydroxyl protecting group

Publications (1)

Publication Number Publication Date
CN116675593A true CN116675593A (en) 2023-09-01

Family

ID=87788405

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202310640948.2A Pending CN116675593A (en) 2023-06-01 2023-06-01 Method for selectively removing hydroxyl protecting group

Country Status (1)

Country Link
CN (1) CN116675593A (en)

Similar Documents

Publication Publication Date Title
CN110117260B (en) Preparation method of 3-alkyl quinoxaline-2 (1H) -ketone compound
Avenoza et al. Enantioselective synthesis of (S)-and (R)-α-methylserines: application to the synthesis of (S)-and (R)-N-Boc-N, O-isopropylidene-α-methylserinals
RU2248348C2 (en) Method for preparing naproxen nitroxyalkyl esters
CN113061077B (en) Alpha, alpha-dideuteroalcohol compounds, deuterated drugs and preparation method thereof
CN116675593A (en) Method for selectively removing hydroxyl protecting group
CN116970030A (en) Cyclic ester peptide reaction intermediate and synthesis method of natural product
WO2006028776A1 (en) Method of synthesis of water soluble fullerene polyacids using a malonate reactant
CN114751849B (en) Preparation method of brivaracetam and intermediate compound
WO2013038206A1 (en) A process
Zefirova et al. Synthetic approach to preparation of polycyclic compounds possessing physiological activity: I. Synthesis of 1, 4-disubstituted adamantanes with amino acid fragment
Maezaki et al. Stereodivergent synthesis of 1, 4-bifunctional compounds by regio-and diastereoselective Pd-catalyzed allylic substitution reaction
BG108759A (en) Process for preparing 2-(substituted phenyl)-2-hydroxy-ethyl carbamates
CN112939830B (en) Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone
CN111635312B (en) Synthesis method of (E) -2-fluoroalkyl-3-butenoate compound
CN117185925B (en) Preparation method of polysubstituted aryl carboxylate compound
CN110156738B (en) Total synthesis method of illitane type sesquiterpene reaction intermediate and natural product
CN112299937B (en) Efficient preparation method of symmetrical diarylethene compound
CN114478373B (en) Preparation method of sulfamate
US10370393B2 (en) Stereoretentive cross-coupling of boronic acids
CN106905098B (en) A kind of synthetic method of neighbour's iodo alpha-acyloxy carbonyls
EP3950663A1 (en) New method for obtaining diester compounds useful for the manufacture of new quaternary ammonium compounds
CN117186005A (en) Fluorene derivative, application and method for preparing same
CN115433097A (en) Method for preparing 4-butoxybenzoic acid (2-diethylaminoethyl) ester without metal
CN114805168A (en) Pyrrolinone compound and synthetic method thereof
US6313353B1 (en) Method for producing an optically active acyloin

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination