US2002177739A1PendingUtilityA1
Method for the preparation of sevoflurane
Assignee: MEDEVA PHARMACEUTICALS PA INCPriority: Aug 18, 1997Filed: Jul 11, 2002Published: Nov 28, 2002
Est. expiryAug 18, 2017(expired)· nominal 20-yr term from priority
Inventors:Ross C. Terrell
C07C 41/22
45
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Claims
Abstract
A method for the preparation of sevoflurane which comprises (a) providing a liquid mixture of (CF 3 ) 2 CHOCH 2 Cl, hydrogen fluoride, and an amine and (b) reacting the mixture, to form (CF 3 ) 2 CHOCH 2 F.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method for the preparation of sevoflurane which comprises:
(a) providing a liquid mixture of (CF 3 ) 2 CHOCH 2 Cl, hydrogen fluoride, and an amine; and (b) reacting the mixture; to form (CF 3 ) 2 CHOCH 2 F.
2 . The method of claim 1 , wherein the mixture is reacted by heating.
3 . The method of claim 1 , wherein the mixture is reacted by heating at 40° C. to 80° C.
4 . The method of claim 1 , wherein the mixture is reacted by heating at 55° C. to 65° C.
5 . The method of claim 1 , wherein the amine is selected from a primary amine, a secondary amine, or a tertiary amine.
6 . The method of claim 5 , wherein the amine is selected from propylamine or diethylamine.
7 . The method of claim 5 , wherein the amine is a tertiary amine.
8 . The method of claim 7 , wherein the tertiary amine is a trialkylamine.
9 . The method of claim 8 , wherein the trialkylamine is selected from triethylamine, tripropylamine, triisopropylamine, tributylamine, dimethyl ethyl amine, di-isopropyl ethyl amine, or mixtures thereof.
10 . The method of claim 1 , wherein the amine is a cyclic amine.
11 . The method of claim 10 , wherein the cyclic amine is selected from pyrrolidine, N-methyl pyrrolidine, or piperidine.
12 . The method of claim 1 , wherein the mixture comprises (CF 3 ) 2 CHOCHCl 2 .
13 . The method of claim 12 , wherein the mixture comprises from 0.01 to 20 percent by weight of (CF 3 ) 2 CHOCHCl 2 .
14 . The method of claim 1 , wherein the mixture comprises water.
15 . The method of claim 14 , wherein the mixture comprises 1 to 25 percent by weight of water.
16 . The method of claim 14 , wherein the mixture comprises 1 to 15 percent by weight of water.
17 . The method of claim 14 , wherein the mixture comprises 3 to 10 percent by weight of water.
18 . The method of claim 1 , wherein the mole ratio of the (CF 3 ) 2 CHOCH 2 Cl to the hydrogen fluoride is from 1:1 to 1:2.
19 . The method of claim 1 , wherein the mole ratio of the (CF 3 ) 2 CHOCH 2 Cl to the amine is from 1:0.3 to 1:2.
20 . The method of claim 3 , wherein the mixture is reacted for 4 to 12 hours.
21 . The method of claim 3 , wherein the mixture is reacted for 4 to 10 hours.
22 . The method of claim 3 , wherein the mixture is reacted for 4 to 7 hours.
23 . The method of claim 1 , wherein the yield of the reaction is at least 50 percent.
24 . The method of claim 1 , wherein the yield of the reaction is at least 65 percent.
25 . The method of claim 1 , wherein the yield of the reaction is at least 75 percent.
26 . The method of claim 1 , wherein the conversion of the reaction is at least 50 percent.
27 . The method of claim 1 , wherein the conversion of the reaction is at least 60 percent.
28 . The method of claim 1 , wherein the conversion of the reaction is at least 70 percent.
29 . The method of claim 1 , comprising separating the (CF 3 ) 2 CHOCH 2 F from the mixture after the mixture has reacted by washing the mixture with water.
30 . The method of claim 1 , comprising separating the (CF 3 ) 2 CHOCH 2 F from the mixture by steam distillation.
31 . The method of claim 1 , comprising separating the (CF 3 ) 2 CHOCH 2 F from the mixture by fractional distillation.
32 . The method of claim 1 , comprising separating the (CF 3 ) 2 CHOCH 2 F from the mixture by distillation with an inert high boiling solvent having a boiling point above that of sevoflurane.
33 . The method of claim 32 , wherein the high boiling solvent is an aromatic hydrocarbon.
34 . The method of claim 33 , wherein the aromatic hydrocarbon is xylene.
35 . The method of claim 32 , wherein the distillation with the inert high boiling solvent proceeds simultaneously with reacting the mixture.
36 . A method for the preparation of sevoflurane which comprises:
(a) providing (CF 3 ) 2 CHOCH 3 ; (b) contacting the (CF 3 ) 2 CHOCH 3 with chlorine gas; (c) exposing the mixture to a sufficient amount of light to initiate and sustain an exothermic reaction; (d) allowing the exothermic reaction to proceed to produce a (CF 3 ) 2 CHOCH 2 Cl intermediate; and (e) reacting in a liquid mixture the (CF 3 ) 2 CHOCH 2 Cl intermediate with hydrogen fluoride and an amine; to form (CF 3 ) 2 CHOCH 2 F.
37 . The method of claim 36 , wherein the (CF 3 ) 2 CHOCH 2 Cl intermediate is reacted with the amine and the hydrogen fluoride by heating.
38 . The method of claim 36 , wherein the (CF 3 ) 2 CHOCH 2 Cl intermediate is reacted with the amine and the hydrogen fluoride by heating at 40° C. to 80° C.
39 . The method of claim 36 , wherein the (CF 3 ) 2 CHOCH 2 Cl intermediate is reacted with the amine and the hydrogen fluoride by heating at 55° C. to 65° C.
40 . The method of claim 36 , wherein the light is ultraviolet light.
41 . The method of claim 36 , wherein the amine is a tertiary amine.
42 . The method of claim 41 , wherein the tertiary amine is selected from triethyl amine, tripropyl amine, triisopropylamine, tributylamine, dimethyl ethyl amine, di-isopropyl ethyl amine, N-methyl pyrrolidine, or mixtures thereof.Join the waitlist — get patent alerts
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