US3769319A - N-ethyl-n-(1 - (m-trifluoromethylphenyl)-propyl-(2))-carbamic acid ethyl ester - Google Patents
N-ethyl-n-(1 - (m-trifluoromethylphenyl)-propyl-(2))-carbamic acid ethyl ester Download PDFInfo
- Publication number
- US3769319A US3769319A US00150169A US3769319DA US3769319A US 3769319 A US3769319 A US 3769319A US 00150169 A US00150169 A US 00150169A US 3769319D A US3769319D A US 3769319DA US 3769319 A US3769319 A US 3769319A
- Authority
- US
- United States
- Prior art keywords
- carbamic acid
- ethyl
- trifluoromethylphenyl
- propyl
- ethyl ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- -1 m-trifluoromethylphenyl Chemical group 0.000 title description 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- 239000001257 hydrogen Substances 0.000 abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 4
- MCSCRFLELPWFHB-UHFFFAOYSA-N (3,3,3-trifluoro-2-phenylpropyl)carbamic acid Chemical class FC(F)(F)C(CNC(O)=O)C1=CC=CC=C1 MCSCRFLELPWFHB-UHFFFAOYSA-N 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000036528 appetite Effects 0.000 description 3
- 235000019789 appetite Nutrition 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 150000001805 chlorine compounds Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical class NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
Definitions
- This invention relates to' new substituted N-(trifluoromethylphenylethyl)-carbamic acid esters of the general formula @oH -h-iI-c-o-R. mo in. ii (I) wherein the trifluoromethyl group may occupy the ortho, meta or para positions on the phenyl ring, R, is hydrogen or a lower alkyl radical with up to 3 carbon atoms, R is hydrogen or a lower alkyl radical with up to 3 carbon atoms with the proviso that if R, is hydrogen, R is an alkyl radical, and R represents an alkyl radical with 1 to 4 carbon atoms.
- the compounds according to the invention exhibit a very good appetite-inhibiting effectiveness, which approximately corresponds tothat of compounds presently used for this purpose in human medicine.
- they do not show any stimulating and motility-increasing effect even in sublethal dosage and are characterized in particular by good compatibility and low toxicity.
- N-ethyl-N-[l-(m-trifluoromethylphenyl)-propyl-(2)]-carbamic acid ethyl ester an LD of 1,000 mg./kg.
- R is hydrogen
- R R and R are defined previously.
- N [Z-methyl-1-(p-trifluoromethylphenyl)-propyl-(2) carbamic acid ethyl ester also has an LD of only ap proximately 2,000 mg./kg.
- the compounds according to the invention are about five to ten times less toxic than N ethyl-l-(m-trifluoromethylphenyl)-propylamine- (2).
- Their appetite-inhibiting etfect is, however, only about two to three times less so that their therapeutic range is two to three times larger. They can, therefore, be handled with'considerably greater safety in human medicine than the preparations used thus far for this purpose.
- N ethyl 1 (m trifiuoromethylphenyl) propylamine- (2) having a boiling point of 98 to 100 C./1O mm. Hg and a refractive index of 11 1.4545 is obtained.
- Part 3 1.0 mole of N-ethyl-l-(m-trifiuoromethylphenyl)-propylamine-(Z) from Part 2 in 96% alcohol is added drop by drop at approximately 0 C. to a solution of 1.1 moles of chloroformic acid ethyl ester in 96% alcohol while stirring and cooling and then, in the course of 20 minutes, it is mixed with an aqueous saturated potassium hydrogen carbonate solution. After stirring for three hours. the alcohol is distilled off, the residue absorbed in ether, dried with sodium sulfate and freed of the ether.
- EXAMPLE 2 6 grams of 2-methyl-l-(p-trifluoromethylphenyll-propylamine-(Z) are dissolved in ethylene chloride and mixed with a solution of 3.1 g. of chloroformic acid ethyl ester in ethylene chloride while stirring. Subsequently an aqueous solution of 2.9 g. of potassium hydrogen carbonate is C. and the reaction mixture added drop by drop at 4-6 C. The separated ethis stirred for several hours at 20 ylene chloride phase is washed with water, filtered and 2.17 g.
- EXAMPLE 4 2.31 g. (0.01 mole) of N-ethyl-l-(m-trifluoromethyl- I phenyl)-propylamlne-(2) are dissolved in benzene. Phos gene is introduced in the presence of some pyridine while pp. 570 and 571 relied on.
- N-ethyl-N-[l- (m trifluoromethylphenyl) propyl (2)]carbamic acid chloride is first taken up in ether and then mixed with ethanol. After shaking with water, drying over sodium sulfate and removal of the solvent and recrystallization in etroleum ether, 2.45 g. (80.7% of the theoretical yield) of N ethyl-N-[1-(mtrifluoromethylphenyl)propyl-(2)1 carbamic acid ethyl ester which is identical'with thecompound obtained in Example 1 are obtained.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15016971A | 1971-06-04 | 1971-06-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3769319A true US3769319A (en) | 1973-10-30 |
Family
ID=22533379
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US787097D Pending USB787097I5 (enrdf_load_stackoverflow) | 1971-06-04 | ||
| US00150169A Expired - Lifetime US3769319A (en) | 1971-06-04 | 1971-06-04 | N-ethyl-n-(1 - (m-trifluoromethylphenyl)-propyl-(2))-carbamic acid ethyl ester |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US787097D Pending USB787097I5 (enrdf_load_stackoverflow) | 1971-06-04 |
Country Status (1)
| Country | Link |
|---|---|
| US (2) | US3769319A (enrdf_load_stackoverflow) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4215139A (en) * | 1978-03-17 | 1980-07-29 | Hoffmann-La Roche Inc. | Carbamic acid derivatives |
| US5587398A (en) * | 1994-06-03 | 1996-12-24 | David R. Elmaleh | Meta substituted arylalkylamines and therapeutic and diagnostic uses therefor |
| US5736573A (en) * | 1996-07-31 | 1998-04-07 | Galat; Alexander | Lipid and water soluble derivatives of drugs |
| US6004990A (en) * | 1994-06-03 | 1999-12-21 | Zebra Pharmaceuticals | Meta substituted arylalkylamines and therapeutic and diagnostic uses therefor |
| EP3170807A1 (en) | 2015-11-23 | 2017-05-24 | Frau Pharma S.r.l. | New method for synthesis of fenfluramine, of isomers therof and/or of analogs thereof, and new compositions comprising it |
-
0
- US US787097D patent/USB787097I5/en active Pending
-
1971
- 1971-06-04 US US00150169A patent/US3769319A/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4215139A (en) * | 1978-03-17 | 1980-07-29 | Hoffmann-La Roche Inc. | Carbamic acid derivatives |
| US5587398A (en) * | 1994-06-03 | 1996-12-24 | David R. Elmaleh | Meta substituted arylalkylamines and therapeutic and diagnostic uses therefor |
| US6004990A (en) * | 1994-06-03 | 1999-12-21 | Zebra Pharmaceuticals | Meta substituted arylalkylamines and therapeutic and diagnostic uses therefor |
| US6313175B1 (en) | 1994-06-03 | 2001-11-06 | Biostream, Inc. | Meta substituted arylalkylamines and therapeutic and diagnostic uses therefor |
| US5736573A (en) * | 1996-07-31 | 1998-04-07 | Galat; Alexander | Lipid and water soluble derivatives of drugs |
| EP3170807A1 (en) | 2015-11-23 | 2017-05-24 | Frau Pharma S.r.l. | New method for synthesis of fenfluramine, of isomers therof and/or of analogs thereof, and new compositions comprising it |
Also Published As
| Publication number | Publication date |
|---|---|
| USB787097I5 (enrdf_load_stackoverflow) |
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