US3944608A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Synthesis of N-[1-(chloromethyl)propyl]acetamide
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 N-[1-(Chloromethyl)propyl]acetamide, 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 N-[1-(chloromethyl)propyl]acetamide. This may be hydrolyzed further 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.
Inventors
- 👤 Balwant Singh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 13:38
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: 9
Claim 1
Independent Claim
59 words
A process for the synthesis of N-[1-(chloromethyl)propyl]acetamide which comprises reacting N-[1-(chloromethyl)propyl]acetimidoyl chloride with water, in the presence of at least about a molar equivalent of a weak base selected from the group consisting of calcium carbonate, calcium oxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, barium carbonate, and strontium carbonate, thereby hydrolyzing N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide.
Claim 2
Dependent Claim
59 words
A process for the synthesis of N-[1-(chloromethyl)propyl]acetamide which comprises reacting N-[1-(chloromethyl)propyl]acetimidoyl chloride with water, in the presence of at least about a molar equivalent of a weak base selected from the group consisting of calcium carbonate, calcium oxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, barium carbonate, and strontium carbonate, thereby hydrolyzing N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide.
Claim 3
Dependent Claim
93 words
In the synthesis of N-[1-(chloromethyl)propyl]acetamide by the reaction of butene-1, chlorine and acetonitrile to form N-[1-(chloromethyl)propyl]acetimidoyl chloride, with the concurrent by-product production of 1,2-dichlorobutane, and the hydrolysis of said N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide, the improvement comprising: adding sufficient water in the presence of at least about a molar equivalent of a weak base selected from the group consisting of calcium carbonate, calcium oxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, barium carbonate, and strontium carbonate to hydrolyze N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide, and distilling off under reduced pressure acetonitrile and 1,2-dichlorobutane.
Claim 4
Dependent Claim
93 words
In the synthesis of N-[1-(chloromethyl)propyl]acetamide by the reaction of butene-1, chlorine and acetonitrile to form N-[1-(chloromethyl)propyl]acetimidoyl chloride, with the concurrent by-product production of 1,2-dichlorobutane, and the hydrolysis of said N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide, the improvement comprising: adding sufficient water in the presence of at least about a molar equivalent of a weak base selected from the group consisting of calcium carbonate, calcium oxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, barium carbonate, and strontium carbonate to hydrolyze N-[1-(chloromethyl)propyl]acetimidoyl chloride to N-[1-(chloromethyl)propyl]acetamide, and distilling off under reduced pressure acetonitrile and 1,2-dichlorobutane.
Claim 5
Dependent Claim
104 words
A process for the synthesis of N-[1-(chloromethyl)propyl]acetamide which comprises 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 in the presence of at least about a molar equivalent of a weak base selected from the group consisting of calcium carbonate, calcium oxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, barium carbonate, and strontium carbonate, 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 6
Dependent Claim
104 words
A process for the synthesis of N-[1-(chloromethyl)propyl]acetamide which comprises 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 in the presence of at least about a molar equivalent of a weak base selected from the group consisting of calcium carbonate, calcium oxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, barium carbonate, and strontium carbonate, 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
50 words
The process of claim 3 in which water is added at about the same rate as N-[1-(chloromethyl)propyl]acetimidoyl chloride is produced, thereby hydrolyzing to 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 4 in which the separated acetonitrile is recycled without additional purification.
Claim 9
Dependent Claim
27 words
The process of claim 5 in which the addition of butene-1, chlorine and water to acetonitrile is a continuous process, and the recycling of acetonitrile is continuous.
References Cited (Backward Citations)
US2569549A
Cited
US3855300A
Cited
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 |