1116-77-4

Basic information

• Product Name: 4,4-Diethoxy-N,N-dimethyl-1-butanamine
• Synonyms: N,N-DIMETHYL-4-AMINOBUTANAL DIETHYL ACETAL;N, N-DIMETHYL-4,4-DIETHOXY-1-BUTANAMINE;1-BUTANAMINE 4,4-DIETHOXY-N,N-DIMETHYL;4-(N,N-DIMETHYLAMINO)BUTANAL DIETHYL ACETAL;4-DIMETHYLAMINO BUTYRALDEHYDE DIETHYL ACETAL;4-DIMETHYLAMINO BUTANAL DIETHYL ACETAL;(4,4-DIETHOXY-BUTYL)-DIMETHYL-AMINE;4,4-DIETHOXY-N,N-DIMETHYL-1-BUTANAMINE
• CAS NO: 1116-77-4
• Molecular Formula: C₁₀H₂₃NO₂
• Molecular Weight: 189.3
• EINECS: 1592732-453-0
• Product Categories: Amines;API intermediates;Intermediates of Rizatriptan;Other Products
• Mol File: 1116-77-4.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 194-195C
• Flash Point: 158 °F
• Appearance: Colorless to light-yellowish lucent liquid
• Density: 0.844 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.0649mmHg at 25°C
• Refractive Index: n20/D 1.421(lit.)
• Storage Temp.: 2-8°C
• Solubility: Chloroform, Ethyl Acetate
• PKA: 9.71±0.28(Predicted)
• CAS DataBase Reference: 4,4-Diethoxy-N,N-dimethyl-1-butanamine(CAS DataBase Reference)
• NIST Chemistry Reference: 4,4-Diethoxy-N,N-dimethyl-1-butanamine(1116-77-4)
• EPA Substance Registry System: 4,4-Diethoxy-N,N-dimethyl-1-butanamine(1116-77-4)

Safety Data

• Hazard Codes: Xi,C
• Statements: 41-34-10-36/37/38
• Safety Statements: 26-36/37/39-16-37
• RIDADR: UN 3267 8 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 1116-77-4(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow liquid

Uses

4,4-Diethoxy-N,N-dimethyl-1-butanamine is used in organic synthesis and pharmaceutical intermediates, it is an intermediate for Sumatriptan, Rizatriptan, Almotriptan, Zolmitriptan.

Application

4-Dimethylaminobutyraldehyde Diethyl Acetal (Zolmitriptan USP Related Compound H) is used in the preparation of N,N-Dimethyltryptamines, 5-HT1D receptor agonists, for medicinal treatments such as antimigraine drugs.

Preparation

4-Dimethylaminobutyraldehyde diethyl acetal synthesis: The reaction of 1-bromo-3-chloro propane and dimethylamine solution with PEG as a phase transfer catalyst, and obtained 3-dimethylamino-1-chloro propane. 3-dimethylamino-1-chloro propane reacted with magnesium and Grinard reagent was acquired. 4-Dimethylaminobutyraldehyde diethyl acetal is obtained by the reaction of Grinard reagent and triethyl orthoformate. The yield was 70.11%.

Synthesis Reference(s)

Tetrahedron Letters, 35, p. 2401, 1994 DOI: 10.1016/0040-4039(94)85230-8

InChI:InChI=1/C10H23NO2/c1-5-12-10(13-6-2)8-7-9-11(3)4/h10H,5-9H2,1-4H3

Synthetic route

3-(Dimethylamino)propyl chloride (109-54-6) + orthoformic acid triethyl ester (122-51-0) → 4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4)

Conditions	Yield
With iodine; magnesium In benzene for 3.25 - 4.33333h; Heating / reflux;	75.8%
With iodine; magnesium In cyclohexane for 5.25 - 6.33333h; Heating / reflux;	72.8%
With magnesium In cyclohexane at 65 - 70℃; for 6h;

diethyl phenyl orthoformate (14444-77-0) + 3-(Dimethylamino)propyl chloride (109-54-6) → 4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4)

Conditions	Yield
Stage #1: 3-(Dimethylamino)propyl chloride With iodine; magnesium In benzene for 3.25 - 4.25h; Heating / reflux; Stage #2: diethyl phenyl orthoformate In benzene for 3h;	72.7%

TMABAL diethyl acetal iodide (1116-78-5) → 4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4)

Conditions	Yield
With ethanolamine

3-(N,N-dimethylamino)propylmagnesium chloride (19070-16-7) + orthoformic acid triethyl ester (122-51-0) → 4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4)

Conditions	Yield
In N,N-dimethyl-formamide

formaldehyd (50-00-0) + 4-aminobutyrylaldehyde diethylacetal (6346-09-4) → 4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4)

Conditions	Yield
With titanium(IV) isopropylate; sodium tetrahydroborate 1.) diglyme, 60 deg C, 30 min then r.t., 30 min; 2.) diglyme, r.t., 2.5 h then 60 deg C, 2.5 h; Yield given. Multistep reaction;

ethanol (64-17-5) + hydrochloride of γ-dimethylamino-butyraldehyde → 4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4)

Conditions	Yield
With hydrogenchloride

4-aminobutyrylaldehyde diethylacetal (6346-09-4) → 4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol; sodium hydrogencarbonate 2: 2-amino-ethanol View Scheme

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + (6Z,9Z,29Z,32Z)-octatriaconta-6,9,29,32-tetraene-18,20-diol → 3-(4-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-6-((9Z,12Z)-octadeca-9,12-dien-1-yl)-1,3-dioxan-2-yl)-N,N-dimethylpropan-1-amine (1427469-90-6)

Conditions	Yield
With pyridinium p-toluenesulfonate In toluene at 80℃; for 1h;	68%

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) → 4-Dimethylamino-butyraldehyde oxime (5929-14-6)

Conditions	Yield
(i) aq. HCl, (ii) NH2OH*HCl, aq. NaOH; Multistep reaction;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) → N,N-dimethyl-4-aminobutyraldehyde (104459-70-3) + 2-Hydroxy-1,1-dimethyl-pyrrolidinium

Conditions	Yield
With sulfuric acid Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) → C16H36N4O2(2+)*2I(1-)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) aq. HCl, (ii) NH2OH*HCl, aq. NaOH 2: dimethylformamide View Scheme

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) → C18H40N4O2(2+)*2Br(1-)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) aq. HCl, (ii) NH2OH*HCl, aq. NaOH 2: dimethylformamide View Scheme

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) → C22H48N4O2(2+)*2Br(1-)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) aq. HCl, (ii) NH2OH*HCl, aq. NaOH 2: dimethylformamide View Scheme

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one hydrochloride → zolmitriptan (139264-17-8)

Conditions	Yield
In water at 90℃; for 3h; Fischer Indole Synthesis; Heating / reflux;
With hydrogenchloride In water Reflux;	62 g
With hydrogenchloride In water Reflux; Large scale;	8.2 kg

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + (4-[1,2,4]triazol-1-ylmethylphenyl)hydrazine hydrochloride → C15H22N6 (1016900-24-5)

Conditions	Yield
With hydrogenchloride In water at 20 - 25℃; for 1h;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + 4-(1H-1,2,4-triazol-1-ylmethyl)phenylhydrazinesulfonic acid (1034806-43-3) → rizatriptan (144034-80-0)

Conditions	Yield
Stage #1: 4,4-diethoxy-N,N-dimethyl-1-butanamine; 4-(1H-1,2,4-triazol-1-ylmethyl)phenylhydrazinesulfonic acid With sulfuric acid In water at 35 - 42℃; for 9h; Fischer Indole cyclization; Stage #2: With sodium hydroxide; water at 0 - 5℃; pH=10.5 - 11; Product distribution / selectivity;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (152305-23-2) → zolmitriptan (139264-17-8)

Conditions	Yield
Stage #1: (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one With hydrogenchloride; sodium nitrite In water at 0℃; for 0.5h; Stage #2: With sodium metabisulfite; sodium hydroxide In water at 2 - 60℃; for 1.25h; Heating / reflux; Stage #3: 4,4-diethoxy-N,N-dimethyl-1-butanamine With hydrogenchloride; sodium hydroxide more than 3 stages;
Stage #1: (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one With hydrogenchloride; sodium nitrite In water at 0℃; for 1.5h; Stage #2: With sodium sulfite In water at 0 - 60℃; Stage #3: 4,4-diethoxy-N,N-dimethyl-1-butanamine
Stage #1: (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 0.5h; Stage #2: With sodium sulfite In water at 10℃; for 0.25h; Stage #3: 4,4-diethoxy-N,N-dimethyl-1-butanamine With hydrogenchloride Product distribution / selectivity; more than 3 stages;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one (187975-62-8) → zolmitriptan (139264-17-8)

Conditions	Yield
at 90 - 98℃; for 2.5h; Product distribution / selectivity; Heating / reflux;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + 4-(1,2,4-triazol-1-ylmethyl)phenylhydrazine (144035-22-3) → rizatriptan (144034-80-0)

Conditions	Yield
Stage #1: 4-(1,2,4-triazol-1-ylmethyl)phenylhydrazine With sulfuric acid In water at 65 - 70℃; for 2h; Fischer Indole Synthesis; Industry scale; Stage #2: 4,4-diethoxy-N,N-dimethyl-1-butanamine In water at 20 - 70℃; Fischer Indole Synthesis; Industry scale; Stage #3: With ammonia In water pH=8.5 - 9; Industry scale;
Stage #1: 4-(1,2,4-triazol-1-ylmethyl)phenylhydrazine With sulfuric acid at 65 - 70℃; for 2h; Fischer Indole Synthesis; Stage #2: 4,4-diethoxy-N,N-dimethyl-1-butanamine at 20 - 70℃; for 3 - 4h; Fischer Indole Synthesis; Stage #3: With ammonia; water at 15 - 20℃; pH=8.5 - 9;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + 4-Hydrazino-N-methylbenzenemethanesulphonamide hydrochloride → C14H24N4O2S (103628-54-2)

Conditions	Yield
With hydrogenchloride In water at 25 - 30℃; for 2h; Product distribution / selectivity; Acidic aqueous solution;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + 4-bromophenylhydrazine hydrochloride (622-88-8) → 5-bromo-3-[2-(N,N-dimethylamino)ethyl]-1H-indole (17274-65-6)

Conditions	Yield
Stage #1: 4,4-diethoxy-N,N-dimethyl-1-butanamine; 4-bromophenylhydrazine hydrochloride With acetic acid In water for 4h; Fischer Indole Synthesis; Reflux; Stage #2: With sodium hydrogencarbonate In water pH=8 - 9;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + 4-(1H-1,2,4-triazol-1-ylmethyl)aniline (119192-10-8) → rizatriptan (144034-80-0)

Conditions	Yield
Stage #1: 4-(1H-1,2,4-triazol-1-ylmethyl)aniline With hydrogenchloride In water at 25 - 30℃; for 0.333333 - 0.5h; Stage #2: With sodium nitrite In water at 0 - 5℃; for 3h; Stage #3: 4,4-diethoxy-N,N-dimethyl-1-butanamine With sulfuric acid; ammonia; sodium sulfite Product distribution / selectivity; more than 3 stages;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + 1-iodo-2-phenylethyne (932-88-7) → 4,4-diethoxy-N-methyl-N-(3-phenylprop-2-yn-1-yl)butan-1-amine

Conditions	Yield
With [Au2(μ-bis(diphenylphosphanyl)methane)2](OTf)2 In acetonitrile at 0 - 20℃; for 4h; Inert atmosphere; Irradiation;

4,4-diethoxy-N,N-dimethyl-1-butanamine (1116-77-4) + 2-acetyloxy-4-methoxy-4′-bromomethyl-benzophenone → N-(4-(2-acetoxy-4-methoxybenzoyl)benzyl)-4,4-diethoxy-N,N-dimethylbutan-1-aminium bromide

Conditions	Yield
In ethyl acetate at 20℃; Inert atmosphere;

Upstream product

• 50-00-0 formaldehyd 
• 6346-09-4 4-aminobutyrylaldehyde diethylacetal 
• 64-17-5 ethanol 
• 14444-77-0 diethyl phenyl orthoformate 
• 109-54-6 3-(Dimethylamino)propyl chloride 
• 122-51-0 orthoformic acid triethyl ester 
• 1116-78-5 TMABAL diethyl acetal iodide 
• 19070-16-7 3-(N,N-dimethylamino)propylmagnesium chloride 

Downstream Products

• 139264-17-8 zolmitriptan 
• 144034-80-0 rizatriptan 
• 17274-65-6 5-bromo-3-[2-(N,N-dimethylamino)ethyl]-1H-indole 
• 103628-54-2 C₁₄H₂₄N₄O₂S 
• 1016900-24-5 C₁₅H₂₂N₆ 
• 104459-70-3 N,N-dimethyl-4-aminobutyraldehyde 

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