Patent US3944619A successfully refreshed from Google Patents.
US3944619A
Expired / Lapsed
US
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Synthesis of d-2-amino-1-butanol
Assignee: Wyeth Holdings LLC
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Filing: 1974-08-01
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Granted: 1976-03-16
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Expires: 1994-08-01
Abstract
Abstract D-2-Amino-1-butanol, for the synthesis of ethambutol hydrochloride, d,d'-2,2'-(ethylenediimino)di-1-butanol dihydrochloride, is produced in high purity and good yields by the reaction of butene-1, a nitrile, preferably an excess of acetonitrile, and chlorine to form N-[1-(chloromethyl)propyl]acetimidoyl chloride which is hydrolyzed to dl-2-amino-1-butanol, which can be isolated as the hydrochloride, or free base, or a mixture, resolved with L(+)- tartaric acid and the d-2-amino-1-butanol reacted with ethylene dichloride and then hydrochloric acid to form ethambutol hydrochloride. A minimum of by-products which are conveniently split out permits the economical synthesis of a pharmaceutical grade product.
Inventors
- 👤 Balwant Singh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 17:27
CPC Classifications
C; C07; C07C; C07C231/00; C07C231/10; C07C233/00; C07C233/01; C07C233/12; C07C233/13; C07C249/00; C07C249/02; C07C257/00; C07C257/02; C07B; C07B2200/00; C07B2200/07; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/582
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
60 words
A process for the isolation of d-2-amino-1-butanol from dl-2-amino-1-butanol containing up to about 10% of dl-1-amino-2-butanol which comprises forming a solution of said dl-2-amino-1-butanol containing dl-1-amino-2-butanol in anhydrous methanol, adding thereto L(+)-tartaric acid in at least about one-half molar quantity, and separating the crystalline acid L(+)-tartrate salt of d-2-amino-1-butanol from the methanol containing 1-2-amino-1-butanol and both d- and l- 1-amino-2-butanol.
Claim 2
Dependent Claim
60 words
A process for the isolation of d-2-amino-1-butanol from dl-2-amino-1-butanol containing up to about 10% of dl-1-amino-2-butanol which comprises forming a solution of said dl-2-amino-1-butanol containing dl-1-amino-2-butanol in anhydrous methanol, adding thereto L(+)-tartaric acid in at least about one-half molar quantity, and separating the crystalline acid L(+)-tartrate salt of d-2-amino-1-butanol from the methanol containing 1-2-amino-1-butanol and both d- and l- 1-amino-2-butanol.
Claim 3
Dependent Claim
52 words
The process of claim 1 in which the dl-2-amino-1-butanol is synthesized by heating N-[1-(chloromethyl)propyl]acetamide in the presence of a lower alkanol and water whereby the N-[1-(chloromethyl)propyl]acetamide is hydrolyzed to dl-2-amino-1-butanol hydrochloride and distilling off the coproduced alkanol acetate, whereby side reactions are suppressed, and the hydrolysis to dl-2-amino-1butanol hydrochloride is essentially quantitative.
Claim 4
Dependent Claim
21 words
The process of claim 2 in which the lower alkanol is methanol, and the dl-2-amino-1-butanol is separated as the hydrochloride salt.
Claim 5
Dependent Claim
23 words
The process of claim 2 in which the N-[1-(chloromethyl)propyl]acetamide is synthesized by reacting N-[1-(chloromethyl)propyl]acetimidoyl chloride with water, thereby hydrolyzing N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide.
Claim 6
Dependent Claim
68 words
The process of claim 2 in which the N-[1-(chloromethyl)propyl]acetamide is synthesized by reacting at least about 2 moles of acetonitrile with about 1 mole of chlorine and about 1 mole of butene-1, to produce N-[1-(chloromethyl)propyl]acetimidoyl chloride with the concurrent production of 1,2-dichlorobutane, adding water, thereby hydrolyzing said N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide, and after the synthesis of said N-[1-chloromethyl)propyl]acetamide, distilling off under reduced pressure and recovering the excess acetonitrile.
Claim 7
Dependent Claim
49 words
The process of claim 5 in which water is added at about the same rate as N-[1-(chloromethyl)propyl]acetimidoyl chloride is produced, thereby hydrolyzing N-[1-(chloromethyl)propyl]acetamide before said N-[1-(chloromethyl)propyl]acetimidoyl chloride can be additionally chlorinated, and also releasing the heat of hydrolysis over the course of the reaction, thus controlling isothermal temperature rise.
Claim 8
Dependent Claim
15 words
The process of claim 6 in which the separated acetonitrile is recycled without additional purification.
Claim 9
Dependent Claim
27 words
The process of claim 7 in which the addition of butene-1, chlorine and water to acetonitrile is a continuous process, and the recycling of acetonitrile is continuous.
Claim 10
Dependent Claim
15 words
The process of claim 5 in which the chlorine, butene-1 and water are added concurrently.
Claim 11
Dependent Claim
18 words
The process of claim 5 in which butene-1 is added first, and then chlorine and water are added.
Claim 12
Dependent Claim
18 words
The process of claim 1 in which about one-third of the dl-2-amino-1-butanol is present as the hydrochloride salt.
Claim 13
Dependent Claim
19 words
The process of claim 5 in which the water is present with the acetonitrile before the addition of chlorine.
Claim 14
Dependent Claim
73 words
In the production of dl-2-amino-1-butanol, or one of its optical isomers, as the free base, from the hydrochloride, the improvement comprising the process of adding an excess of NH 3 to precipitate HCl as NH 4 Cl, evaporating off excess NH 3 , and separating out the NH 4 Cl, whereby there is neither excess NH 3 or HCl remaining in the product free base of dl-amino-1-butanol, or one of its optical isomers.
Claim 15
Dependent Claim
73 words
In the production of dl-2-amino-1-butanol, or one of its optical isomers, as the free base, from the hydrochloride, the improvement comprising the process of adding an excess of NH 3 to precipitate HCl as NH 4 Cl, evaporating off excess NH 3 , and separating out the NH 4 Cl, whereby there is neither excess NH 3 or HCl remaining in the product free base of dl-amino-1-butanol, or one of its optical isomers.
Claim 16
Dependent Claim
74 words
In the production of dl-2-amino-1-butanol, or one of its optical isomers, as the free base, from the hydrochloride, the improvement comprising the process of adding an excess of NH 3 to precipitate HCl as NH 4 Cl, separating out the NH 4 Cl, and evaporating off the excess NH 3 , whereby there is neither excess NH 3 or HCl remaining in the product free base of dl-amino-1-butanol, or one of its optical isomers.
Claim 17
Dependent Claim
74 words
In the production of dl-2-amino-1-butanol, or one of its optical isomers, as the free base, from the hydrochloride, the improvement comprising the process of adding an excess of NH 3 to precipitate HCl as NH 4 Cl, separating out the NH 4 Cl, and evaporating off the excess NH 3 , whereby there is neither excess NH 3 or HCl remaining in the product free base of dl-amino-1-butanol, or one of its optical isomers.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-03-16 | 1979-09-15 | 1980-03-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-03-16 | 1983-09-15 | 1984-03-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-03-16 | 1987-09-15 | 1988-03-16 | $7700.00 | Window Closed / Lapsed |