US4914220A
Expired / Lapsed
US
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Process for synthesis of E-2-methyl-α,β-unsaturated aldehydes
Assignee: Merck and Co Inc
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Filing: 1989-02-27
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Granted: 1990-04-03
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Expires: 2009-02-27
Abstract
Abstract A process is described for the synthesis of E-2-methyl-α,β-unsaturated aldehydes, which are useful as intermediates in the synthesis of the macrolide structure of the immunosuppressant FK-506. These compounds are also useful as ultraviolet radiation absorbers.
Inventors
- 👤 Richard Desmond
- 👤 Sander G. Mills
- 👤 Ralph P. Volante
- 👤 Ichiro Shinkai
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 06:56
CPC Classifications
C; C07; C07C; C07C45/00; C07C45/51; C07C45/516; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804; C07F7/1872; C07F7/1888; C07F7/1892
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
152 words
A process comprising the steps of: (a) contacting the aldehyde I: ##STR29## where P is a triorganosilyl protecting group, with the imine lithium salt IIa: ##STR30## where R 1 , R 2 , R 3 are independently selected from C 1 -C 4 linear or branched alkyl or phenyl, and R 4 is C 3 -C 8 secondary or tertiary alkyl, phenyl or substituted phenyl; in an inert organic solvent at -80° C. to -20° C. for a sufficient time to form a mixture of imines III and IV; ##STR31## (b) contacting the mixture of imines III and IV from step (a) with anhydrous trifluoroacetic acid at a temperature of -10° C. to +25° C. for a sufficient time to substantially convert imine III (Z) to imine IV (E); and (c) contacting the resulting mixture from step (b) with water at a temperature of -0° C. to +25° C. to form ##STR32##
Claim 2
Dependent Claim
152 words
A process comprising the steps of: (a) contacting the aldehyde I: ##STR29## where P is a triorganosilyl protecting group, with the imine lithium salt IIa: ##STR30## where R 1 , R 2 , R 3 are independently selected from C 1 -C 4 linear or branched alkyl or phenyl, and R 4 is C 3 -C 8 secondary or tertiary alkyl, phenyl or substituted phenyl; in an inert organic solvent at -80° C. to -20° C. for a sufficient time to form a mixture of imines III and IV; ##STR31## (b) contacting the mixture of imines III and IV from step (a) with anhydrous trifluoroacetic acid at a temperature of -10° C. to +25° C. for a sufficient time to substantially convert imine III (Z) to imine IV (E); and (c) contacting the resulting mixture from step (b) with water at a temperature of -0° C. to +25° C. to form ##STR32##
Claim 3
Dependent Claim
40 words
The process of claim 1 wherein the temperature in step (a) is -80° C. to -60° C., the temperature in step (b) is -5° C. to +5° C., and the temperature in step (c) is 0° C. to 5° C.
Claim 4
Dependent Claim
17 words
The process of claim 1 wherein P is selected from triisopropylsilyl, triethylsilyl, t-butyldimethylsilyl, triphenylsilyl, tribenzylsilyl, or t-butyldiphenylsilyl.
Claim 5
Dependent Claim
9 words
The process of claim 3 wherein P is triisopropylsilyl.
Claim 6
Dependent Claim
25 words
The process of claim 1 wherein R 1 , R 2 , R 3 are independently selected from methyl, ethyl, isopropyl, t-butyl, phenyl or benzyl.
Claim 7
Dependent Claim
17 words
The process of claim 5 wherein R 1 , R 2 , R 3 are all ethyl.
Claim 8
Dependent Claim
18 words
The process of claim 1 wherein R 4 is cyclopentyl, cyclohexyl, thexyl, t-pentyl, t-hexyl, phenyl, o-tolyl and 2,6-dimethylphenyl.
Claim 9
Dependent Claim
10 words
The process of claim 7 wherein R 4 is cyclohexyl.
Claim 10
Dependent Claim
78 words
A process comprising the steps of (a) contacting a mixture of imines III and IV where R 4 is C 3 -C 8 secondary or tertiary alkyl with anhydrous trifluoroacetic acid at a temperature of -10° C. to +25° C. for a sufficient time to substantially convert imine III (Z) to imine IV (E); and ##STR33## (b) contacting the resulting mixture from step (a) with water at a temperature of -5° C. to +25° C. to form ##STR34##
Claim 11
Dependent Claim
78 words
A process comprising the steps of (a) contacting a mixture of imines III and IV where R 4 is C 3 -C 8 secondary or tertiary alkyl with anhydrous trifluoroacetic acid at a temperature of -10° C. to +25° C. for a sufficient time to substantially convert imine III (Z) to imine IV (E); and ##STR33## (b) contacting the resulting mixture from step (a) with water at a temperature of -5° C. to +25° C. to form ##STR34##
Claim 12
Dependent Claim
29 words
The process of claim 9 wherein the temperature in step (a) is -10° C. to +25° C., and the temperature in step (b) is -5° C. to +25° C.
Claim 13
Dependent Claim
17 words
The process of claim 9 wherein P is selected from triisopropylsilyl, triethylsilyl, t-butyldimethylsilyl, triphenylsilyl, tribenzylsilyl, or t-butyldiphenylsilyl.
Claim 14
Dependent Claim
9 words
The process of claim 11 wherein P is triisopropylsilyl.
Claim 15
Dependent Claim
25 words
The process of claim 9 wherein R 1 , R 2 , R 3 are independently selected from methyl, ethyl, isopropyl, t-butyl, phenyl or benzyl.
Claim 16
Dependent Claim
17 words
The process of claim 9 wherein R 1 , R 2 , R 3 are all ethyl.
Claim 17
Dependent Claim
18 words
The process of claim 9 wherein R 4 is cyclopentyl, cyclohexyl, thexyl, t-pentyl, t-hexyl, phenyl, o-tolyl or 2,6-dimethylphenyl.
Claim 18
Dependent Claim
10 words
The process of claim 7 wherein R 4 is cyclohexyl.
References Cited (Backward Citations)
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