CN106631902A - Method for preparing telavancin side chain 9H-fluoren-9-ylmethyl decyl(2-oxoethyl)carbamate - Google Patents
Method for preparing telavancin side chain 9H-fluoren-9-ylmethyl decyl(2-oxoethyl)carbamate Download PDFInfo
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- CN106631902A CN106631902A CN201610843257.2A CN201610843257A CN106631902A CN 106631902 A CN106631902 A CN 106631902A CN 201610843257 A CN201610843257 A CN 201610843257A CN 106631902 A CN106631902 A CN 106631902A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
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Abstract
The invention discloses a method for preparing telavancin side chain 9H-fluoren-9-ylmethyl decyl(2-oxoethyl)carbamate. The preparation method comprises the following steps: (1) taking n-decanol as an initial raw material, and carrying out oxidation to obtain a n-decanal compound; (2)carrying out reduction amination on the obtained n-decanal compound to obtain N-decyl aminoacetaldehyde dimethyl acetal hydrochloride compound; (3) performing two-step synthesis on N-decyl aminoacetaldehyde dimethyl acetal hydrochloride compound to obtain 9H-fluoren-9-ylmethyl decyl(2-oxoethyl)carbamate compound, wherein the step (3) comprises Fmoc protection and hydrolysis of acetal. The method has the advantages of cheap raw materials, low cost, safe and simple operation, great applicability, being convenient to popularize and apply, and a wide prospect of large-scale industrial application.
Description
Technical field
The invention belongs to chemical medicine field, is specifically related to a kind of Te Lawan stars side chain decyl (2- oxoethyls) amino
The preparation method of formic acid 9H- fluorenes -9- methyl esters.
Background technology
Te Lawan stars (Telavancin) are a kind of LG antibiotic, are ratified for treating gram positive bacteria by FDA
The complexity skin for causing and skin structure infection (complicated skin and skin structure
Infections, cSSSI), this time expand the Nosocomial bacterial pneumonia that indication causes for Staphylococcus aureus
(hospital-acquired bacterial pneumonia, HABP) and Ventilator Acquired bacterial pneumonia
(ventilator-associated bacterial pneumonia,VABP).And decyl (2- oxoethyls) carbamic acid
9H- fluorenes -9- methyl esters have vital effect as side chain in the synthesis of Te Lawan stars.
WO0039156 reports Te Lawan star side chains：Decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters
Synthetic method, its synthetic route one：With positive decanoyl chloride 2 as initiation material, first it is condensed with glycine methyl ester hydrochloride 3, Ran Houjing
Aluminium lithium hydrogen reduction, then upper Fmoc protections, it is finally oxidized to obtain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters
1, it is synthesized through 4 steps, such as shown in figure (1).Synthetic route two：With n-Decylamine 7 as initiation material, first 2,2- dimethoxy second
The reduction amination of aldehyde 8, then goes up Fmoc protections, and last hydrolysis of acetals obtains decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- first
Base ester 1, such as shown in figure (2).
Said method respectively has advantage, but all exists：Initiation material is difficult acquisition, financial cost height, and part operation is dangerous
Property high defect, be unfavorable for that technique is amplified.It is therefore desirable to exploring, new, step is few, low cost decyl (2- oxo second
Base) carbamic acid 9H- fluorenes -9- methyl esters synthetic route.
The content of the invention
The technical problem to be solved is to provide a kind of Te Lawan stars side chain decyl (2- oxoethyls) amino
The preparation method of formic acid 9H- fluorenes -9- methyl esters, the synthetic method solves and make in prior art cost of material height, is difficult to obtain
Obtain and synthesize the above-mentioned problems such as complexity.
The technical problem to be solved employs the following technical solutions to realize：
A kind of preparation method of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters, the system
Preparation Method is comprised the following steps：
(1) it is oxidized with Decanol as initiation material, obtain n-capric aldehyde compound；
(2) gained n-capric aldehyde compound Jing reduction aminations, obtain the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal hydrochloride compounds of N-；
(3) the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds of gained N- synthesize through two steps, obtain decyl (2- oxoethyls)
Carbamic acid 9H- fluorenes -9- methyl ester compounds.
The present invention further improvement is that：In the step (1), solvent is dichloromethane, and oxidant is 2,2,6,6- tetra-
Methyl piperidine oxide and liquor natrii hypochloritis.
The present invention further improvement is that：In the step (1), reaction temperature is -10～50 DEG C.
The present invention further improvement is that：In the step (1), reaction temperature is 0～25 DEG C.
The present invention further improvement is that：In the step (2), solvent is fatty alcohol, and catalyst is palladium carbon.
The present invention further improvement is that：In the step (2), solvent is methyl alcohol, ethanol, propyl alcohol and butanol.
The present invention further improvement is that：In the step (2), reaction temperature is 20～100 DEG C.
The present invention further improvement is that：In the step (2), solvent is methyl alcohol, and reaction temperature is 40～50 DEG C.
The present invention further improvement is that：In the step (3), including upper Fmoc protections and hydrolysis of acetals.
The invention has the beneficial effects as follows：This kind of Te Lawan star side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- first
The synthetic method of base ester, it is first oxidized to obtain n-capric aldehyde with Decanol as initiation material, then reduce with 2,2- dimethoxy-ethylamines
Amination, then goes up Fmoc protections, and last hydrolysis of acetals obtains decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters；Its
Make inexpensive raw material, low cost, safe operation simple, application is strong, easy to utilize, with the wide of large-scale industrial application
Wealthy prospect.
Description of the drawings
Fig. 1 is the synthetic technology of existing Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters
(1) schematic flow sheet；
Fig. 2 is the synthetic technology of existing Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters
(2) schematic flow sheet；
Fig. 3 is the conjunction of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters of the present invention
Into techniqueflow schematic diagram.
Specific embodiment
In order that technological means, creation characteristic, reached purpose and effect that the present invention is realized are easy to understand, tie below
Conjunction is specifically illustrating, and the present invention is expanded on further.
As shown in figure 3, a kind of system of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters
Preparation Method, the preparation method is comprised the following steps：
(1) it is oxidized with Decanol 11 as initiation material, obtain n-capric aldehyde compound 12；
(2) the Jing reduction aminations of gained n-capric aldehyde compound 12, obtain the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal hydrochloride chemical combination of N-
Thing 14；
(3) the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 of gained N- synthesize through two steps, obtain decyl (2- oxo second
Base) carbamic acid 9H- fluorenes -9- methyl ester compounds 1.
Wherein, in the step (3), including upper Fmoc protections and hydrolysis of acetals.
Specific embodiment one：
(1) synthesis of n-capric aldehyde compound 12
Plus Decanol 11 (60g, 380mmol), 2,2,6,6- tetramethyl piperidine oxides (TEMPO) (0.5g, 3mmol) and
In the there-necked flask of dichloromethane (1200mL) a to 3000mL, stir to complete molten, while being cooled to 0 DEG C；In -10 DEG C of conditions
Under, 7.5% liquor natrii hypochloritis (500g) and 5% sodium bicarbonate solution (600g) is added dropwise, -10 DEG C (temperature range for -10～
50 DEG C) stirring 6h (duration scope is 2～6h)；Reaction is finished, and 10% sodium sulfite solution (600g), layering is added dropwise；Organic phase
It is dried, is concentrated to give weak yellow liquid, i.e. n-capric aldehyde compound 12 (52g, yield 88%).
(2) synthesis of the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 of N-
Plus n-capric aldehyde 12 (30g, 192mmol), 2,2- dimethoxy-ethylamines 13 (20.1g, 192mmol) and methyl alcohol
(300mL) in the hydriding reactor of a 1L, under nitrogen protection, 2h is stirred at 20 DEG C (duration scope is 1～2h)；Add 5% palladium
Carbon (0.6g), Hydrogen Vapor Pressure 0.5MPa, in 20 DEG C of (temperature range is 20～100 DEG C) stirring 6h (duration scope is 2～6h)；Instead
Should finish, reaction solution is filtered, add hydrochloric acid, filtrate reduced in volume, and faint yellow solid, i.e. N- are obtained through acetone recrystallization
Positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compound 14 (18.9g, yield 35%).
(3) synthesis of decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters 1
A, upper Fmoc protect amine
Plus the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 (18.9g, 67mmol) of N-, DIPEA
(DIPEA) (11.4g, 90mmol) and dichloromethane (200mL) are cooled to -10 DEG C in the there-necked flask of a 500mL；- 10
Fluorenes methoxy dicarbonyl chloride (11.6g, 90mmol) and dichloromethane (50ml) solution are added dropwise under DEG C (temperature range be -10～-20 DEG C),
Completion of dropping, in 0 DEG C of (temperature range is 0～30 DEG C) stirring 4h (duration scope is 2～4h)；Reaction is finished, and 5% chlorination is added dropwise
Hydrogen solution (200ml), layering；Organic phase is dried, and is concentrated to give weak yellow liquid 10；
B, hydrolysis of acetals
Dichloromethane (300ml) will be added in gained weak yellow liquid 10 in above-mentioned a, into the there-necked flask of a 500mL,
- 10 DEG C are cooled to, 37% hydrochloric acid (77g, 0.75mol) is added dropwise under -10 DEG C (temperature range is -10～-20 DEG C)；Drip
Finish, in 10 DEG C of (temperature range is 10～30 DEG C) stirring 4h (duration scope is 2～4h)；Reaction is finished, and 5% sodium acid carbonate is added dropwise
Solution (300ml)；Layering, organic phase is dried；Concentration, normal heptane is recrystallized to give white solid, i.e. decyl (2- oxoethyls)
Carbamic acid 9H- fluorenes -9- methyl esters (20.3g, yield 82.2%).
Specific embodiment two：
(1) synthesis of n-capric aldehyde compound 12
Plus Decanol 11 (60g, 380mmol), 2,2,6,6- tetramethyl piperidine oxides (TEMPO) (0.5g, 3mmol) and
In the there-necked flask of dichloromethane (1200mL) a to 3000mL, stir to complete molten, while being cooled to 0 DEG C；Under the conditions of 0 DEG C,
7.5% liquor natrii hypochloritis (500g) and 5% sodium bicarbonate solution (600g) are added dropwise, 0 DEG C (temperature range is -10～50 DEG C)
Stirring 5h (duration scope is 2～6h)；Reaction is finished, and 10% sodium sulfite solution (600g), layering is added dropwise；Organic phase is dried,
It is concentrated to give weak yellow liquid, i.e. n-capric aldehyde compound 12 (52g, yield 88%).
(2) synthesis of the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 of N-
Plus n-capric aldehyde 12 (30g, 192mmol), 2,2- dimethoxy-ethylamines 13 (20.1g, 192mmol) and ethanol
(300mL) in the hydriding reactor of a 1L, under nitrogen protection, 1.7h is stirred at 40 DEG C (duration scope is 1～2h)；Add 5%
Palladium carbon (0.6g), Hydrogen Vapor Pressure 0.5MPa, 40 DEG C (temperature range be 20～100 DEG C) stirring 3.5h (duration scope is 2～
6h)；Reaction is finished, and reaction solution is filtered, and adds hydrochloric acid, filtrate reduced in volume, and obtains pale yellow colored solid through acetone recrystallization
Body, i.e. N- positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compound 14 (18.9g, yield 35%).
(3) synthesis of decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters 1
A, upper Fmoc protect amine
Plus the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 (18.9g, 67mmol) of N-, DIPEA
(DIPEA) (11.4g, 90mmol) and dichloromethane (200mL) are cooled to -10 DEG C in the there-necked flask of a 500mL；- 12
Fluorenes methoxy dicarbonyl chloride (11.6g, 90mmol) and dichloromethane (50ml) solution are added dropwise under DEG C (temperature range be -10～-20 DEG C),
Completion of dropping, in 10 DEG C of (temperature range is 0～30 DEG C) stirring 3h (duration scope is 2～4h)；Reaction is finished, and 5% chlorine is added dropwise
Change hydrogen solution (200ml), layering；Organic phase is dried, and is concentrated to give weak yellow liquid 10；
B, hydrolysis of acetals
Dichloromethane (300ml) will be added in gained weak yellow liquid 10 in above-mentioned a, into the there-necked flask of a 500mL,
- 10 DEG C are cooled to, 37% hydrochloric acid (77g, 0.75mol) is added dropwise under -12 DEG C (temperature range is -10～-20 DEG C)；Drip
Finish, in 15 DEG C of (temperature range is 10～30 DEG C) stirring 3h (duration scope is 2～4h)；Reaction is finished, and 5% sodium acid carbonate is added dropwise
Solution (300ml)；Layering, organic phase is dried；Concentration, normal heptane is recrystallized to give white solid, i.e. decyl (2- oxoethyls)
Carbamic acid 9H- fluorenes -9- methyl esters (20.3g, yield 82.2%).
Specific embodiment three：
(1) synthesis of n-capric aldehyde compound 12
Plus Decanol 11 (60g, 380mmol), 2,2,6,6- tetramethyl piperidine oxides (TEMPO) (0.5g, 3mmol) and
In the there-necked flask of dichloromethane (1200mL) a to 3000mL, stir to complete molten, while being cooled to 0 DEG C；Under the conditions of 25 DEG C,
7.5% liquor natrii hypochloritis (500g) and 5% sodium bicarbonate solution (600g) are added dropwise, (temperature range is -10～50 at 25 DEG C
DEG C) stirring 3.5h (duration scope is 2～6h)；Reaction is finished, and 10% sodium sulfite solution (600g), layering is added dropwise；Organic phase
It is dried, is concentrated to give weak yellow liquid, i.e. n-capric aldehyde compound 12 (52g, yield 88%).
(2) synthesis of the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 of N-
Plus n-capric aldehyde 12 (30g, 192mmol), 2,2- dimethoxy-ethylamines 13 (20.1g, 192mmol) and propyl alcohol
(300mL) in the hydriding reactor of a 1L, under nitrogen protection, 1.3h is stirred at 50 DEG C (duration scope is 1～2h)；Add 5%
Palladium carbon (0.6g), Hydrogen Vapor Pressure 0.5MPa, 50 DEG C (temperature range be 20～100 DEG C) stirring 4.5h (duration scope is 2～
6h)；Reaction is finished, and reaction solution is filtered, and adds hydrochloric acid, filtrate reduced in volume, and obtains pale yellow colored solid through acetone recrystallization
Body, i.e. N- positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compound 14 (18.9g, yield 35%).
(3) synthesis of decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters 1
A, upper Fmoc protect amine
Plus the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 (18.9g, 67mmol) of N-, DIPEA
(DIPEA) (11.4g, 90mmol) and dichloromethane (200mL) are cooled to -10 DEG C in the there-necked flask of a 500mL；- 17
Fluorenes methoxy dicarbonyl chloride (11.6g, 90mmol) and dichloromethane (50ml) solution are added dropwise under DEG C (temperature range be -10～-20 DEG C),
Completion of dropping, in 20 DEG C of (temperature range is 0～30 DEG C) stirring 2.5h (duration scope is 2～4h)；Reaction is finished, and is added dropwise 5%
Hydrogen chloride solution (200ml), layering；Organic phase is dried, and is concentrated to give weak yellow liquid 10；
B, hydrolysis of acetals
Dichloromethane (300ml) will be added in gained weak yellow liquid 10 in above-mentioned a, into the there-necked flask of a 500mL,
- 10 DEG C are cooled to, 37% hydrochloric acid (77g, 0.75mol) is added dropwise under -17 DEG C (temperature range is -10～-20 DEG C)；Drip
Finish, in 25 DEG C of (temperature range is 10～30 DEG C) stirring 2.5h (duration scope is 2～4h)；Reaction is finished, and 5% bicarbonate is added dropwise
Sodium solution (300ml)；Layering, organic phase is dried；Concentration, normal heptane is recrystallized to give white solid, i.e. decyl (2- oxo second
Base) carbamic acid 9H- fluorenes -9- methyl esters (20.3g, yield 82.2%).
Specific embodiment four：
(1) synthesis of n-capric aldehyde compound 12
Plus Decanol 11 (60g, 380mmol), 2,2,6,6- tetramethyl piperidine oxides (TEMPO) (0.5g, 3mmol) and
In the there-necked flask of dichloromethane (1200mL) a to 3000mL, stir to complete molten, while being cooled to 0 DEG C；Under the conditions of 50 DEG C,
7.5% liquor natrii hypochloritis (500g) and 5% sodium bicarbonate solution (600g) are added dropwise, (temperature range is -10～50 at 50 DEG C
DEG C) stirring 2h (duration scope is 2～6h)；Reaction is finished, and 10% sodium sulfite solution (600g), layering is added dropwise；It is organic relevant
It is dry, it is concentrated to give weak yellow liquid, i.e. n-capric aldehyde compound 12 (52g, yield 88%).
(2) synthesis of the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 of N-
Plus n-capric aldehyde 12 (30g, 192mmol), 2,2- dimethoxy-ethylamines 13 (20.1g, 192mmol) and butanol
(300mL) in the hydriding reactor of a 1L, under nitrogen protection, 1h is stirred at 100 DEG C (duration scope is 1～2h)；Add 5% palladium
Carbon (0.6g), Hydrogen Vapor Pressure 0.5MPa, in 100 DEG C of (temperature range is 20～100 DEG C) stirring 2h (duration scope is 2～6h)；
Reaction is finished, and reaction solution is filtered, and adds hydrochloric acid, filtrate reduced in volume, and obtains faint yellow solid through acetone recrystallization, i.e.,
The positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 of N- (18.9g, yield 35%).
(3) synthesis of decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters 1
A, upper Fmoc protect amine
Plus the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds 14 (18.9g, 67mmol) of N-, DIPEA
(DIPEA) (11.4g, 90mmol) and dichloromethane (200mL) are cooled to -10 DEG C in the there-necked flask of a 500mL；- 20
Fluorenes methoxy dicarbonyl chloride (11.6g, 90mmol) and dichloromethane (50ml) solution are added dropwise under DEG C (temperature range be -10～-20 DEG C),
Completion of dropping, in 30 DEG C of (temperature range is 0～30 DEG C) stirring 2h (duration scope is 2～4h)；Reaction is finished, and 5% chlorine is added dropwise
Change hydrogen solution (200ml), layering；Organic phase is dried, and is concentrated to give weak yellow liquid 10；
B, hydrolysis of acetals
Dichloromethane (300ml) will be added in gained weak yellow liquid 10 in above-mentioned a, into the there-necked flask of a 500mL,
- 10 DEG C are cooled to, 37% hydrochloric acid (77g, 0.75mol) is added dropwise under -20 DEG C (temperature range is -10～-20 DEG C)；Drip
Finish, in 30 DEG C of (temperature range is 10～30 DEG C) stirring 2h (duration scope is 2～4h)；Reaction is finished, and 5% sodium acid carbonate is added dropwise
Solution (300ml)；Layering, organic phase is dried；Concentration, normal heptane is recrystallized to give white solid, i.e. decyl (2- oxoethyls)
Carbamic acid 9H- fluorenes -9- methyl esters (20.3g, yield 82.2%).
The present invention provides the conjunction of this kind of Te Lawan star side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl ester
Into method, inexpensive raw material, low cost, safe operation are made simply, application is strong, easy to utilize, with large-scale industry
Using bright prospects.
The basic principles, principal features and advantages of the present invention have been shown and described above.The technical staff of the industry should
Understand, the present invention is not restricted to the described embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification
Reason, without departing from the spirit and scope of the present invention, the present invention also has various changes and modifications, these changes and improvements
Both fall within scope of the claimed invention.The claimed scope of the invention is by appending claims and its equivalent circle.
It is fixed.
Claims (9)
1. a kind of preparation method of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl esters, its feature
It is：The preparation method is comprised the following steps：
(1) it is oxidized with Decanol as initiation material, obtain n-capric aldehyde compound；
(2) gained n-capric aldehyde compound Jing reduction aminations, obtain the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal hydrochloride compounds of N-；
(3) the positive last of the ten Heavenly stems aminoacetaldehyde dimethyl acetal compounds of gained N- synthesize through two steps, obtain decyl (2- oxoethyls) amino
Formic acid 9H- fluorenes -9- methyl ester compounds.
2. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl according to claim 1
The preparation method of ester, it is characterised in that：In the step (1), solvent is dichloromethane, and oxidant is 2,2,6,6- tetramethyl piperazines
Pyridine oxide and liquor natrii hypochloritis.
3. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- according to claim 1 and 2
The preparation method of methyl ester, it is characterised in that：In the step (1), reaction temperature is -10～50 DEG C.
4. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl according to claim 3
The preparation method of ester, it is characterised in that：In the step (1), reaction temperature is 0～25 DEG C.
5. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl according to claim 1
The preparation method of ester, it is characterised in that：In the step (2), solvent is fatty alcohol, and catalyst is palladium carbon.
6. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl according to claim 5
The preparation method of ester, it is characterised in that：In the step (2), solvent is methyl alcohol, ethanol, propyl alcohol and butanol.
7. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- according to claim 5 or 6
The preparation method of methyl ester, it is characterised in that：In the step (2), reaction temperature is 20～100 DEG C.
8. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl according to claim 7
The preparation method of ester, it is characterised in that：In the step (2), solvent is methyl alcohol, and reaction temperature is 40～50 DEG C.
9. a kind of Te Lawan stars side chain decyl (2- oxoethyls) carbamic acid 9H- fluorenes -9- methyl according to claim 1
The preparation method of ester, it is characterised in that：In the step (3), including upper Fmoc protections and hydrolysis of acetals.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111233713A (en) * | 2020-01-20 | 2020-06-05 | 福建康鸿生物科技有限公司 | Synthesis method of telavancin intermediate |
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| CN111233713A (en) * | 2020-01-20 | 2020-06-05 | 福建康鸿生物科技有限公司 | Synthesis method of telavancin intermediate |
| CN114213284A (en) * | 2022-01-04 | 2022-03-22 | 丽珠集团福州福兴医药有限公司 | (9H-fluorene-9-yl) -decyl (2-oxoethyl) methyl carbamate and synthetic method thereof |
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