CN106866567A - The synthetic method of fluoro Oxazolidinone derivative - Google Patents

The synthetic method of fluoro Oxazolidinone derivative Download PDF

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CN106866567A
CN106866567A CN201710128901.2A CN201710128901A CN106866567A CN 106866567 A CN106866567 A CN 106866567A CN 201710128901 A CN201710128901 A CN 201710128901A CN 106866567 A CN106866567 A CN 106866567A
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CN106866567B (en
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陆红健
阳斌
李子博
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Nanjing University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/44—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/06—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings
    • C07D265/08—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D265/10—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen atoms directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The invention discloses the synthetic method of a class fluoro Oxazolidinone derivative.This method provide the ketone of oxazolidine 2 for directly preparing various fluorinations in a mild condition, the diketone of oxazolidine 2,4 and 1, the method for the ketone of 3 oxazines alkane 2.Simultaneously because high price fluorination reagent derives from fluorine anion, therefore the method can apply to Radiofluorinated Oxazolidinone derivative and prepare.The present invention is fluorinated cyclization strategies and has carried out the ketone of fluorination oxazolidine 2 by intramolecular, and the fluorination diketone of oxazolidine 2,4 is effectively synthesized with the fluorination ketone of 1,3 oxazines alkane 2.The reaction has extensive substrate spectrum, the tolerance of various functional groups, and can be used in building the molecular structure with bioactivity.

Description

The synthetic method of fluoro Oxazolidinone derivative
Technical field
The present invention relates to synthesizing activity organic molecule field, and in particular to the conjunction of a class fluoro Oxazolidinone derivative Into method.
Background technology
Compound containing alkene structures carries out intramolecular fluoro cyclization can be built including tool including C-F keys with a step There is the cyclic structure of multiple new keys, its universal architecture unit that can serve as building the fluorine-containing bioactive compound of aliphatic. In the synthetic method reported, it is one of most important method to be cyclized using the fluoro of electrophilic fluorination reagent.However, electrophilic fluorination Reagent is generally prepared by fluorine gas, and preparation cost is high, which has limited it in industry and laboratory, is particularly existed18F radioactivity marks Application in note.Recently, in the research of fluoro cyclization, hypervalent iodine reagent has obtained extensive concern as Fluorine source, because The reactivity of uniqueness is shown for them, and readily can be obtained from cheap fluoride.Alkane is used in these reactions The alkene and styrene derivative of base substitution are used as effective nucleopilic reagent, and the substrate for carrying electron-deficient double bond carries out fluoro ring The reaction of change has no document report.The disease that oxazolidine -2- keto analogs effectively can treat bacterium infection and trigger simultaneously. For example, N- aryl-oxazolidine -2- ketone is considered as the last line of defense for resisting gram-positive bacterium pathogen, these diseases Substance including the antibiotic including methicillin and vancomycin to generating resistance.
The content of the invention
The purpose of the present invention is to be applied to silver-colored catalytic cyclization/1,2- (miscellaneous) aryl migration/fluorine using high price fluorine iodine compound Change cascade reaction, so as to efficiently and compactly synthesize various fluorination Oxazolidinone derivatives.
To reach above-mentioned purpose, the technical scheme that the present invention is provided is：
A kind of fluoro Oxazolidinone derivative, its structural formula is as follows：
Specially：
The synthetic method of described fluoro Oxazolidinone derivative specifically includes following：
Using styrene or acrylamide derivative fluorine cyclization synthesizing fluoro oxazole is carried out with high price fluorine iodine reagent Alkane ketone compounds
By substrate 2, the desired amount of compound 1 (1.5 equivalent), AgSbF6Or AgBF4(0.1 equivalent) and DCM are introduced and added To in reaction bulb.And mixture is stirred at a temperature of 20-60 DEG C, the carrying out of reaction is monitored by TLC.Knot is reacted when observing Beam, reactant mixture is concentrated to dryness, and isolated Oxazolidinone derivative 3 is extracted by column chromatography.
Synthetic product includes：
Synthetic reaction has：
Further, the high price fluorine iodine reagent is including the skeleton structure and derivative including compound 1.
Our initial experiment is used to the fluorine iodine compound 1 of air and moisture stabilization as Fluorine source (table 1), its quilt recently For the research of styrene and the ionic fluoro cyclization of alkyl substituted olefine derivative.Compound 1 using fluoride with Prepared by its chloro or the analog of OTs substitutions, it is applicable to carrier-free addition18The Radiofluorinated reactions of F- are ground Study carefully.As shown in table 1, from unsaturated urethane, (2)s can obtain the oxazolidine -2- ketone of fluorination.Sieved by condition Choosing, it has been found that use AgSbF6Used as catalyst, raw material 2a can obtain fluorination N- aryl-oxazole with 79% separation yield Alkane -2- ketone (3a).Use other metallic catalysts, such as AgBF4, AgOTf and AgF2Product (the bar of low yield can only be obtained Mesh 3-6), and a small amount of water presence can substantially reduce the reactivity (entry 7) of raw material.When the extra fluorine anion of addition When, product 3a (entry 8) is not observed in the presence of AgOTf.Ag catalyst is not added with, or only adds molecular sieve, all do not had Have to form required product 3a.
The reaction condition of table 1. is screened
After obtaining optimum reaction condition, we start to study the range of application of reaction substrate (table 2).We are first First attempt changing the aryl substituent on N atoms, it is found that the reaction all has to electron rich aryl and electron-deficient aryl good Functional group's tolerance (3a-f), can obtain N- aryl-oxazolidine -2- ketone with medium to good yield.Functional group on phenyl Such as halogen, (3c, e), (3a, f) etc. functional group can be compatible with reaction well for ester group (3d) and methoxyl group.Additionally, alkyl-substituted Substrate (3g-1) shows good reactivity in the method, can obtain target product with the yield of 66-78%.Then, Influence we have also investigated aromatics migrating group (3j-t) to reacting.Research finds to replace base and suction with electron on phenyl ring Electron substituent group can effectively occur aryl migration (3j-p).Although the migration performance of 9H- carbazoles is poor (3t), other are miscellaneous Aryl such as thienyl and furyl (3q-s), are the effective mobilities being used as first in being cyclized by the fluoro of high price fluorine iodine reagent induction Group.It has been investigated that, the substituent R in substrate2Influence to reacting is smaller (3u-v).In addition to terminal olefin, internal olefin (Z) -2w is also used as substrate, and target product (3w) is obtained with medium yield.Using alkyl-substituted alkene as substrate, energy Fluorination oxazolidine -2- ketone (3x) is accessed, has no that alkyl is migrated.Product except that can obtain 5 yuan of rings, can also be by the party Method smoothly prepares 6 cyclic products (3y), and it is the key structure in a kind of novel antiretroviral and anti-bacterial drug.
The derivative of the styrene of table 2.a
We have found that the acrylamide of phenyl substitution can also be obtained under improved reaction condition using the catalyst system and catalyzing Corresponding product.Our substrate spectrums to acrylamide have carried out simple research, as a result as shown in table 3, spread out with styrene Biology is similar, and it is all good migrating group that electrophilic or electron-donating group and heterocycle are carried on phenyl ring, finally with medium Yield obtains product oxazolidine -2,4- diketone (3 ').Use of acrylamide as the high price fluorine iodine reagent mediation of nucleopilic reagent Document report is had no before fluoro cyclisation, this is also the special character of the method.
The reaction of the acrylamide derivative of table 3.
Beneficial effect：
The present invention is fluorinated cyclization strategies and has carried out fluorination oxazolidine -2- ketone by intramolecular, is fluorinated oxazolidine -2,4- diketone With being effectively synthesized for fluorination 1,3- oxazines alkane -2- ketone.The reaction has an extensive substrate spectrum, the tolerance of various functional groups, And can be used in building the molecular structure with bioactivity.
Specific embodiment
With reference to specific embodiment, the invention will be further described.
Using styrene or acrylamide derivative fluorine cyclization synthesizing fluoro oxazole is carried out with high price fluorine iodine reagent Alkane ketone compounds
By substrate 2, the desired amount of compound 1 (1.5 equivalent), AgSbF6Or AgBF4(0.1 equivalent) and DCM are introduced and added To in reaction bulb.And mixture is stirred at 20-60 DEG C, the carrying out of reaction is monitored by TLC.When observe reaction terminate, Reactant mixture is concentrated to dryness, isolated Oxazolidinone derivative 3 is extracted by column chromatography.
Synthetic product includes：
The yield of specific each product, identification are as follows：
Prepare 5-Benzyl-5-fluoro-3- (4-methoxyphenyl) oxazolidin-2-one (3a)
CDCl3)δ-92.52ppm.13C NMR(101MHz,CDCl3) δ 156.96,152.32 (d, J=1.7Hz), 132.23 (d, J= 4.2Hz), 130.37,130.20,128.95,128.03,120.68,114.49,112.31 (d, J=233.1Hz), 55.58, 54.10 (d, J=30.6Hz), 42.03 (d, J=29.1Hz) ppm.IR (KBr) ν 3005,2990,1771,1515,1456, 1339,1275,1360,1080,828,764,750,704.HRMS(ESI)m/z calcd.for C17H16FNNaO3 +(M+Na+):324.1006,Found:324.1002.
5-Benzyl-5-fluoro-3-(p-tolyl)oxazolidin-2-one(3b)
CDCl3)δ-92.40ppm.13C NMR(101MHz,CDCl3) δ 152.13,134.70,132.25 (d, J=4.3Hz), (d, J=233.1Hz), 130.42,129.86,129.04,128.11,118.69,112.31 53.77 (d, J=30.7Hz), 42.15 (d, J=29.1Hz), 20.90ppm.IR (KBr) ν 3033,3006,2986,2921,2851,1774,1517,1468, 1404,1335,1275,1261,1080,976,810,764,750,702.HRMS(ESI)m/z calcd.for C17H16FNNaO2 +(M+Na+):308.1057,Found:308.1045.
5-Benzyl-3-(4-chlorophenyl)-5-fluorooxazolidin-2-one(3c)
MHz,CDCl3) δ 151.90,135.81,132.00 (d, J=4.2Hz), 130.39,130.18,129.36,129.08, (d, J=233.9Hz), 128.20,119.66,112.24 53.51 (d, J=30.8Hz), 42.03 (d, J=28.9Hz) ppm.IR(KBr)ν3005,2986,1771,1496,1338,1275,1261,1094,1080,978,826,764,750, 704.HRMS(ESI)m/z calcd.for C16H14ClFNO2 +(M+H+):306.0692,Found:306.0688.
Methyl4-(5-benzyl-5-fluoro-2-oxooxazolidin-3-yl)benzoate(3d)
3.49–3.30(m,2H)ppm.19F NMR(376MHz,CDCl3)δ-92.28ppm.13C NMR(101MHz,CDCl3)δ (d, J=4.2Hz), 166.44,151.72,141.16,131.93 131.01,130.41,129.14,128.27,126.24, (d, J=234.1Hz), 117.51,112.27 53.36 (d, J=30.8Hz), 52.27,42.06 (d, J=28.9Hz) ppm.IR (KBr)ν3033,3004,2951,2920,2849,1778,1717,1608,1517,1497,1281,1187,1112,980, 853,767,748,703.HRMS(ESI)m/z calcd.for C18H16FNNaO4 +(M+Na+):352.0956,Found: 352.0956.
5-Benzyl-3-(3-bromophenyl)-5-fluorooxazolidin-2-one(3e)
19F NMR(376MHz,CDCl3)δ-92.30ppm.13C NMR(101MHz,CDCl3)δ151.73,138.48,131.95(d,J =4.3Hz), 130.62,130.39,129.11,128.23,127.83,123.08,121.27,116.89,112.26 (d, J= 234.0Hz), 53.39 (d, J=30.8Hz), 42.00 (d, J=28.8Hz) ppm.IR (KBr) ν 3004,2990,2920, 2849,1779,1593,1482,1339,1275,1261,1080,992,938,764,750,700.HRMS(ESI)m/z calcd.for C16H14BrFNO2 +(M+H+):350.0186,Found:350.0184.
5-Benzyl-3-(3,5-dimethoxyphenyl)-5-fluorooxazolidin-2-one(3f)
CDCl3) δ 161.37,151.87,139.05,132.15 (d, J=4.3Hz), 130.40,129.05,128.14,112.18 (d, ), J=233.2Hz 97.21,96.67,55.63,53.77 (d, J=30.7Hz), 42.08 (d, J=29.1Hz) ppm.IR (KBr)ν3005,2984,1771,1596,1456,1275,1261,1205,1156,1012,764,750,704.HRMS(ESI) m/z calcd.for C18H18FNNaO4 +(M+Na+):354.1112Found:354.1112
5-Benzyl-3-cyclopentyl-5-fluorooxazolidin-2-one(3g)
CDCl3) δ 7.37-7.27 (m, 5H), 4.16 (p, J=8.1Hz, 1H), 3.57-3.18 (m, 4H), 1.95-1.82 (m, 1H), 1.81–1.69(m,1H),1.67–1.50(m,4H),1.50–1.39(m,1H),1.36–1.24(m,1H)ppm.19F NMR (376MHz,CDCl3)δ-93.00ppm.13C NMR(101MHz,CDCl3) δ 154.64,132.54 (d, J=4.3Hz), (d, J=232.5Hz), 130.29,128.83,127.85,113.11 54.47,49.57 (d, J=30.4Hz), 42.20 (d, J =29.6Hz), 29.37,28.68,23.89,23.81ppm.IR (KBr) ν 3005,2989,1771,1456,1275,1260, 1040,908,765,704.HRMS(ESI)m/z calcd.for C15H18FNNaO2 +(M+Na+):286.1214,Found: 286.1214.
5-Benzyl-5-fluoro-3-(thiophen-3-ylmethyl)oxazolidin-2-one(3h)
10.8Hz, 1H), 3.46,3.37 (ABq, J=10.8Hz, 1H), 3.32-3.17 (m, 2H) ppm.19F NMR(376MHz, CDCl3)δ-93.09ppm.13C NMR(101MHz,CDCl3) δ 154.74,137.07,132.29 (d, J=4.7Hz), (d, J=233.9Hz), 130.33,128.86,127.88,127.20,127.12,126.22,113.10 52.03 (d, J= 30.3Hz), 42.38,42.07 (d, J=29.4Hz) ppm.IR (KBr) ν 3005,2989,1776,1473,1275,1261, 1029,897,765,750,703.HRMS(ESI)m/z calcd.for C15H15FNO2S+(M+H+):292.0802,Found: 292.0807.
Ethyl2-(5-benzyl-5-fluoro-2-oxooxazolidin-3-yl)-3-phenylpropanoate (3i)
2.81 (m, 1H), [1.23 (t, J=7.1Hz), 1.18 (t, J=7.1Hz), (3H)] ppm.19F NMR(376MHz,CDCl3)δ- 92.12,-94.35ppm.13C NMR(101MHz,CDCl3) δ 169.95,169.81,155.15 (d, J=1.5Hz), 154.92 (d, J=1.4Hz), 135.71,135.63,132.33 (d, J=3.2Hz), 132.31 (d, J=4.7Hz), 130.38, 130.30,128.92,128.89,128.85,128.81,128.69,128.54,127.89,127.85,127.36,127.29, 113.42 (d, J=234.4Hz), 113.38 (d, J=234.5Hz), 61.92,61.83,56.63,56.54,50.60 (d, J= 29.6Hz), 50.48 (d, J=30.7Hz), 42.18 (d, J=28.9Hz), 42.06 (d, J=29.5Hz), 35.48,35.18, 14.14ppm.IR(KBr)ν3005,2989,1779,1738,1456,1275,1261,1031,897,765,750,703.HRMS (ESI)m/z calcd.for C21H22FNNaO4 +(M+Na+):394.1425,Found:394.1425.
5-([1,1'-Biphenyl]-4-ylmethyl)-5-fluoro-3-(4-methoxyphenyl) oxazolidin-2-one(3j)
3.78(s,3H),3.55–3.29(m,2H)ppm.19F NMR(376MHz,CDCl3)δ-92.48ppm.13C NMR(101MHz, CDCl3) δ 157.01,152.33,140.99,140.53,131.20 (d, J=4.1Hz), 130.81,130.24,128.95, (d, J=233.2Hz), 127.67,127.63,127.17,120.70,114.54,112.32 55.62,54.20 (d, J= 30.6Hz), 41.75 (d, J=29.2Hz) ppm.IR (KBr) ν 3006,2919,2849,1765,1748,1520,1470, 1275,1259,1158,824,764,750,692.HRMS(ESI)m/z calcd.for C23H21FNO3 +(M+H+): 378.1500,Found:378.1495.
5-Fluoro-5-(4-fluorobenzyl)-3-(4-methoxyphenyl)oxazolidin-2-one(3k)
δ 162.64 (d, J=246.9Hz), 157.06,152.23,132.03 (d, J=8.1Hz), 130.13,127.96 (t, J= 3.7Hz), 120.72,115.93 (d, J=21.4Hz), 114.56,112.07 (dd, J=233.0,1.2Hz), 55.63, 54.19 (d, J=30.6Hz), 41.32 (d, J=29.6Hz) ppm.IR (KBr) ν 3008,2992,2920,2845,1771, 1760,1512,1275,1258,1080,826,764,750.HRMS(ESI)m/z calcd.for C17H16F2NO3 +(M+H+): 320.1093,Found:320.1091.
5-Fluoro-5-(4-methoxybenzyl)-3-(4-methoxyphenyl)oxazolidin-2-one(3l)
CDCl3)δ-92.77ppm.13C NMR(101MHz,CDCl3)δ159.46,157.00,152.40,131.46,130.31, 124.19 (d, J=4.6Hz), 120.69,114.55,114.43,112.49 (d, J=232.9Hz), 55.64,55.41, 54.04 (d, J=30.6Hz), 41.23 (d, J=29.4Hz) ppm.IR (KBr) ν 3005,2984,1771,1515,1456, 1339,1275,1260,764,750.HRMS(ESI)m/z calcd.for C18H18FNNaO4 +(M+Na+):354.1112, Found:354.1104.
5-Fluoro-3-(4-methoxyphenyl)-5-(4-(trifluoromethyl)benzyl)oxazolidin- 2-one(3m)
MHz,CDCl3)δ-62.69,-92.86ppm.13C NMR(101MHz,CDCl3) δ 157.18,152.07 (d, J=1.7Hz), 136.22 (dd, J=3.2,1.3Hz), 130.84 (d, J=0.8Hz), 130.52 (q, J=32.6Hz), 130.03,125.93 (q, J=3.7Hz), 124.10 (q, J=272.1Hz), 120.80,114.63,111.72 (d, J=233.4Hz), 55.66, 54.46 (d, J=30.6Hz), 42.02 (d, J=29.5Hz) ppm.IR (KBr) ν 3005,2990,1759,1275,1261, 1159,1123,825,764,750.HRMS(ESI)m/z calcd.for C18H16F4NO3 +(M+H+):370.1061,Found: 370.1065.
5-Fluoro-3-(4-methoxyphenyl)-5-(3-methylbenzyl)oxazolidin-2-one(3n)
3.78(s,3H),3.42–3.22(m,2H),2.36(s,3H)ppm.19F NMR(376MHz,CDCl3)δ-92.42ppm.13C NMR(101MHz,CDCl3) δ 156.92,152.36,138.66,132.12 (d, J=4.1Hz), 131.13,130.24, (d, J=233.1Hz), 128.81,128.78,127.35,120.64,114.48,112.38 55.60,54.06 (d, J= 30.6Hz), 41.95 (d, J=29.0Hz), 21.49ppm.IR (KBr) ν 3005,2989,1771,1515,1457,1339, 1275,1260,1086,764,750,706.HRMS(ESI)m/z calcd.for C18H18FNNaO3 +(M+Na+): 338.1163,Found:338.1162.
5-Fluoro-5-(2-methoxybenzyl)-3-phenyloxazolidin-2-one(3o)
(ABq, J=11.0Hz, 1H), 3.88 (s, 3H), 3.54-3.37 (m, 2H) ppm.19F NMR(376MHz,CDCl3)δ- 91.60ppm.13C NMR(101MHz,CDCl3) δ 157.56,152.26 (d, J=2.0Hz), 137.48,132.80,129.48, (d, J=5.1Hz), 129.31,124.70,121.27,120.72 118.49,112.77 (d, J=233.2Hz), 111.00, (d, J=30.4Hz), 55.70,53.53 34.98 (d, J=30.1Hz) ppm.IR (KBr) ν 3391,3004,2920,2849, 1778,1646,1601,1503,1496,1468,1406,1336,1248,752,696,669.HRMS(ESI)m/z calcd.for C17H16FNNaO3 +(M+Na+):324.1006,Found:324.0998.
5-(3,5-Dimethylbenzyl)-5-fluoro-3-(4-methoxyphenyl)oxazolidin-2-one (3p)
CDCl3)δ-92.25ppm.13C NMR(101MHz,CDCl3) δ 156.97,152.44,138.53,132.08 (d, J= 4.2Hz), 130.34,129.69,128.16,120.70,114.53,112.48 (d, J=233.0Hz), 55.64,54.10 (d, ), J=30.6Hz 41.93 (d, J=28.9Hz), 21.38ppm.IR (KBr) ν 3005,2988,1771,1515,1457,1339, 1275,1260,1086,1067,764,750.HRMS(ESI)m/z calcd.for C19H20FNNaO3 +(M+Na+): 352.1319,Found:352.1314.
5-Fluoro-3-(4-methoxyphenyl)-5-(thiophen-3-ylmethyl)oxazolidin-2-one (3q)
3.49–3.32(m,2H)ppm.19F NMR(376MHz,CDCl3)δ-92.91ppm.13C NMR(101MHz,CDCl3)δ (d, J=4.4Hz), 157.00,152.27,132.24 130.18,128.99,126.64,124.68,120.72,114.53, 112.05 (d, J=232.9Hz), 55.62,54.19 (d, J=30.5Hz), 36.79 (d, J=30.7Hz) ppm.IR (KBr) ν 2920,2849,1771,1646,1515,1469,1338,1276,1255,1090,1060,830,764,750.HRMS(ESI) m/z calcd.for C15H15FNO3S+(M+H+):308.0751,Found:308.0742.
5-Fluoro-3-(4-methoxyphenyl)-5-(thiophen-2-ylmethyl)oxazolidin-2-one (3r)
3.79(s,3H),3.67–3.51(m,2H)ppm.19F NMR(376MHz,CDCl3)δ-93.23ppm.13C NMR(101MHz, CDCl3) δ 157.10,152.14,133.14 (d, J=5.2Hz), 130.17,128.56,127.47,126.20,120.82, (d, J=233.3Hz), 114.59,111.68 55.65,54.00 (d, J=30.4Hz), 36.57 (d, J=32.4Hz) ppm.IR (KBr)ν3006,2920,2849,1775,1646,1515,1469,1338,1275,1257,975,829,764,750.HRMS (ESI)m/z calcd.for C15H15FNO3S+(M+H+):308.0751,Found:308.0747.
5-Fluoro-5-(furan-3-ylmethyl)-3-(4-methoxyphenyl)oxazolidin-2-one(3s)
10.9Hz, 1H), 3.94,3.90 (ABq, J=10.9Hz, 1H), 3.79 (s, 3H), 3.29-3.11 (m, 2H) ppm.19F NMR (376MHz,CDCl3)δ-93.33ppm.13C NMR(101MHz,CDCl3)δ157.13,152.28,143.81,141.47, (d, J=4.9Hz), 130.28,120.79,116.06 114.63,112.10 (d, J=232.6Hz), 111.69,55.66, 54.28 (d, J=30.6Hz), 32.20 (d, J=31.7Hz) ppm.IR (KBr) ν 3392,3006,2920,2849,1771, 1646,1515,1469,1338,1251,1092,1024,874,749.HRMS(ESI)m/z calcd.for C15H15FNO4 +(M +H+):292.0980,Found:292.0967.
5-Fluoro-3-(4-methoxyphenyl)-5-((9-phenyl-9H-carbazol-3-yl)methyl) oxazolidin-2-one(3t)
3.65–3.46(m,2H)ppm.19F NMR(376MHz,CDCl3)δ-92.29ppm.13C NMR(101MHz,CDCl3)δ 156.91152.48,141.39,140.63,137.60,130.36,130.08,128.11,127.79,127.20,126.48, (d, J=4.4Hz), 123.87123.58 122.99,122.12,120.59,120.54,120.29,114.50,112.82 (d, J =232.9Hz), 110.31,110.09,55.63,54.03 (d, J=30.7Hz), 42.10 (d, J=29.1Hz) ppm.IR (KBr)ν3055,3006,2955,2930,2835,1774,1597,1514,1503,1458,1333,1251,1234,1151, 977,937,828,763,749,698.HRMS(ESI)m/z calcd.for C29H23FN2NaO3 +(M+Na+):489.1585, Found:489.1583.
5-Benzyl-5-fluoro-3-(4-methoxyphenyl)-4-methyloxazolidin-2-one(3u)
- 3.16 (m, 2H), [1.27 (d, J=6.7Hz), 1.03 (dd, J=6.5,2.4Hz), (3H)] ppm.19F NMR(376MHz, CDCl3)δ-93.67,-111.55ppm.13C NMR(101MHz,CDCl3) δ 158.37,157.89,153.47 (d, J= 1.4Hz), 152.40 (d, J=1.6Hz), 132.32,132.27,130.58 (d, J=1.2Hz), 130.51,128.87, 128.58,128.41,127.95,127.87,127.61,126.06,124.52,114.74,114.65,114.52 (d, J= 232.8Hz), 113.64 (d, J=238.9Hz), 62.40 (d, J=31.4Hz), 59.18 (d, J=25.7Hz), 55.60, (d, J=29.6Hz), 55.58,41.87 38.78 (d, J=26.4Hz), 14.78 (d, J=9.1Hz), 12.41 (d, J= 12.0Hz)ppm.IR(KBr)
338.1163.
5-Benzyl-4-ethyl-5-fluoro-3-(4-methoxyphenyl)oxazolidin-2-one(3v)
49.4mg, 75%yield, dr=1.5:1.White solid,Mp100-104℃.1H NMR(400MHz, CDCl3)δ7.44–7.29(m,6H),7.06–6.97(m,1H),6.94–6.89(m,1H),6.89–6.84(m,1H),[4.35 (ddd, J=18.8,5.6,4.2Hz), 4.03 (ddd, J=20.4,9.2,3.9Hz), (1H)], [3.80 (s), 3.77 (s), (3H)],3.55–3.09(m,2H),1.90–1.56(m,2H),0.95–0.85(m,3H)ppm.19F NMR(376MHz,CDCl3) δ-90.21,-111.31ppm.13C NMR(101MHz,CDCl3)δ158.47,157.69,153.38,152.81,132.47(d, ), J=7.4Hz 132.28,130.71,130.59 (d, J=0.9Hz), 129.06,128.89,128.56,128.22, (d, J=232.6Hz), 127.93,127.61,126.32,124.19,114.68,114.66,114.26 113.92 (d, J= 239.1Hz), 66.52 (d, J=29.5Hz), 63.72 (d, J=24.9Hz), 55.59,55.56,43.27 (d, J= 30.9Hz), 38.67 (d, J=26.4Hz), 21.56 (d, J=8.9Hz), 20.85 (d, J=10.7Hz), 9.95 (d, J= 2.4Hz),8.61ppm.IR(KBr)ν3006,2986,2921,2851,1776,1515,1456,1403,1275,1259, 1125,1032,978,829,764,750,701.HRMS(ESI)m/z calcd.for C19H21FNO3 +(M+H+): 330.1500,Found:330.1500.
5-Fluoro-3-(4-methoxyphenyl)-5-(1-phenylethyl)oxazolidin-2-one(3w)
MHz,CDCl3)δ-97.07,-106.34ppm.13C NMR(101MHz,CDCl3) δ 157.00,156.95,152.54 (d, J= 1.7Hz), 152.43,138.48 (d, J=4.7Hz), 138.33,130.27,130.22,129.00,128.97,128.79, 128.74 (d, J=2.0Hz), 128.12,128.08,120.79,120.69,114.51,114.49,113.87 (d, J= 234.9Hz), 113.65 (d, J=237.8Hz), 55.63,54.49 (d, J=30.9Hz), 53.46 (d, J=31.1Hz), 46.50 (d, J=26.2Hz), 45.21 (d, J=27.6Hz), 14.98 (d, J=5.0Hz), 14.87 (d, J=3.9Hz) ppm.IR(KBr)ν3005,2989,2918,2849,1773,1514,1463,1406,1337,1275,
18.4mg, 44%yield.Colorless oil.1HNMR(400MHz,CDCl3) δ 7.54 (d, J=8.1Hz, 2H), 7.38 (t, J=7.9Hz, 2H), 7.15 (t, J=7.4Hz, 1H), 4.57,4.43 (ABq, J=9.9Hz, 1H), 4.45,4.32 (ABq, J= 9.9Hz, 1H), 4.09 (d, J=8.9Hz, 1H), 3.76 (dd, J=9.0,1.4Hz, 1H), 1.56 (d, J=2.1Hz, 3H) ppm.19F NMR(376MHz,CDCl3)δ-227.85ppm.13C NMR(101MHz,DMSO)δ153.44,138.29,128.92, (d, J=174.2Hz), 123.57,117.98,85.80 77.19 (d, J=17.5Hz), 51.19 (d, J=5.2Hz), 21.00 (d, J=4.8Hz) ppm.IR (KBr) ν 3005,2989,2920,2851,1749,1460,1414,1322,1275,1261, 1119,897,763,750,706.HRMS(ESI)m/z calcd.for C11H12FNNaO2 +(M+Na+):232.0744, Found:232.0737.
6-Benzyl-6-fluoro-3-(4-methoxyphenyl)-1,3-oxazinan-2-one(3y)
-101.73ppm.13C NMR(101MHz,CDCl3) δ 158.66,150.16,135.14,133.39 (d, J=4.9Hz), (d, J=226.8Hz), 130.60,128.74,127.69,127.23,114.75,113.29 55.63,44.73 (d, J= 26.2Hz), 44.52 (d, J=4.5Hz), 28.43 (d, J=26.0Hz) ppm.IR (KBr) ν 3005,2989,2916,1719, 1512,1478,1426,1275,1260,1164,832,763,750,705.HRMS(ESI)m/z calcd.for C18H18FNNaO3 +(M+Na+):338.1163,Found:338.1157.
5-Benzyl-5-fluoro-3-phenyloxazolidine-2,4-dione(3′a)
150.78,130.62,129.79,129.68,129.59,129.18,128.65,125.58,110.06 (d, J=244.5Hz), 38.91 (d, J=28.2Hz) ppm.
5-Benzyl-3-(4-chlorophenyl)-5-fluorooxazolidine-2,4-dione(3′b)
34.6mg, 54%yield.White solid, Mp136-139 DEG C of1H NMR(400MHz,CDCl3)δ7.41– 7.33(m,5H),7.32–7.28(m,2H),7.02–6.94(m,2H),3.62–3.51(m,2H)ppm.19F NMR(376MHz, CDCl3)δ-110.11ppm.13C NMR(101MHz,CDCl3) δ 165.23 (d, J=24.4Hz), 150.40,135.56, (d, J=10.4Hz), 130.58,129.82,129.60 129.21,128.71,128.21,126.70,110.09 (d, J= 245.1Hz), 38.91 (d, J=28.1Hz) ppm.IR (KBr) ν 3005,2987,2922,2847,1842,1765,1500, 1426,1275,1260,825,764,750,699.HRMS(EI)m/z calcd.for C16H11ClFNO3 +:319.0406, Found:319.0406
3-(4-Chlorophenyl)-5-(3,5-dimethylbenzyl)-5-fluorooxazolidine-2,4- dione(3′c)
19F NMR(376MHz,CDCl3)δ-110.37ppm.13C NMR(101MHz,CDCl3) δ 165.43 (d, J=24.6Hz), (d, J=10.2Hz), 150.50,138.83,135.55,130.25,129.83,129.39 128.35,128.25,126.72, 110.19 (d, J=245.0Hz), 38.79 (d, J=27.7Hz), 21.31ppm.
3-(4-Chlorophenyl)-5-fluoro-5-(4-fluorobenzyl)oxazolidine-2,4-dione (3′d)
(m,4H),3.61–3.46(m,2H).19F NMR(376MHz,CDCl3)δ-109.62,-112.81ppm.13C NMR(101MHz, CDCl3) δ 165.11 (d, J=24.5Hz), 162.93 (d, J=248.4Hz), 150.33,135.65,132.35 (d, J= 8.2Hz), 129.91,128.17,126.56,125.37 (dd, J=10.3,3.4Hz), 116.25 (d, J=21.6Hz), 109.72 (dd, J=244.7,1.7Hz), 37.99 (d, J=28.6Hz) ppm.
3-(4-Chlorophenyl)-5-fluoro-5-(4-methoxybenzyl)oxazolidine-2,4-dione (3′e)
δ 165.35 (d, J=24.5Hz), 159.83,150.50,135.51,131.71,129.81,128.26,126.69,121.28 (d, J=10.8Hz), 114.57,110.15 (d, J=245.3Hz), 55.43,37.98 (d, J=28.1Hz) ppm.
3-(4-Chlorophenyl)-5-fluoro-5-(thiophen-3-ylmethyl)oxazolidine-2,4- dione(3′f)
(101MHz,CDCl3) δ 165.29 (d, J=24.5Hz), 150.47,135.64,129.89,129.59 (d, J=10.9Hz), (d, J=245.4Hz), 128.91,128.23,127.17,126.76,126.01,109.69 33.52 (d, J=29.6Hz) ppm.IR(KBr)ν3005,2989,1765,1501,1457,1427,1275,1261,763,750,706.HRMS(EI)m/z calcd.for C14H9ClFNO3S+:324.9970,Found:324.9969.
The above, is only presently preferred embodiments of the present invention, and any formal limitation is not made to the present invention, any ripe Professional and technical personnel is known, it is without departing from the scope of the present invention, real to more than according to technical spirit of the invention Apply any simple modification, equivalent that example made and improve etc., still fall within technical solution of the present invention protection domain it It is interior.

Claims (3)

1. a kind of fluoro Oxazolidinone derivative, it is characterised in that its structural formula is as follows：
Specially：
2. it is according to claim 1 fluorination Oxazolidinone derivative synthetic method, it is characterised in that utilize styrene Or acrylamide derivative carries out fluorine cyclization synthesizing fluoro Oxazolidinone derivative with high price fluorine iodine reagent, specifically By substrate 2, compound 1, AgSbF6Or AgBF4It is added in reaction bulb with DCM and mixture is stirred at 20-60 DEG C, is led to Cross TLC monitoring reaction carrying out, when observe reaction terminate, reactant mixture is concentrated to dryness, by column chromatography extract point From obtaining Oxazolidinone derivative 3；
Specific reaction equation is as follows：
Its synthetic product includes：
3. synthetic method according to claim 2, it is characterised in that：The high price fluorine iodine reagent, is to include that compound 1 exists Interior skeleton structure and derivative.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109265408A (en) * 2018-12-11 2019-01-25 上海皓元生物医药科技有限公司 The synthetic method of difluoromethyl substitution oxane -2- ketone
CN112939883A (en) * 2019-11-26 2021-06-11 兰州大学 Preparation method of polysubstituted 1, 3 oxazolidine compound
CN113603653A (en) * 2021-08-23 2021-11-05 南通大学 Synthesis method of visible light-promoted selenooxazolidine-2.4-dione
CN114437106A (en) * 2020-10-31 2022-05-06 复旦大学 Method for preparing 1, 3-oxazine-2-ketone derivative by continuous one-pot method

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109265408A (en) * 2018-12-11 2019-01-25 上海皓元生物医药科技有限公司 The synthetic method of difluoromethyl substitution oxane -2- ketone
CN112939883A (en) * 2019-11-26 2021-06-11 兰州大学 Preparation method of polysubstituted 1, 3 oxazolidine compound
CN112939883B (en) * 2019-11-26 2024-01-16 兰州大学 Preparation method of polysubstituted 1, 3-oxazolidine compound
CN114437106A (en) * 2020-10-31 2022-05-06 复旦大学 Method for preparing 1, 3-oxazine-2-ketone derivative by continuous one-pot method
CN114437106B (en) * 2020-10-31 2024-01-05 复旦大学 Method for preparing 1, 3-oxazine-2-ketone derivative by continuous one-pot method
CN113603653A (en) * 2021-08-23 2021-11-05 南通大学 Synthesis method of visible light-promoted selenooxazolidine-2.4-dione
CN113603653B (en) * 2021-08-23 2022-05-13 南通大学 Synthesis method of selenooxazolidine-2, 4-dione promoted by visible light

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