Process for making tertiary aminoalcohol compounds
View Patent ↗Provided is a process for making a tertiary aminoalcohol compound. The process comprises using an excess amount of a carbonyl compound in a condensation step between the carbonyl compound and a nitroalkane, and conducting a hydrogenation/alkylation step to produce the tertiary aminoalcohol. The process uses fewer steps than conventional processes.
1. A process for making a tertiary aminoalcohol compound of formula I:
wherein R 2 is H or C 1 -C 6 alkyl;
R 5 is H, C 1 -C 6 alkyl, or C 3 -C 12 cycloalkyl, or R 2 and R 5 together with the carbon to which they are attached form C 3 -C 12 cycloalkyl;
R 3 and R 4 are independently C 1 -C 6 alkyl, C 3 -C 12 cycloalkyl, or —C(OH)R 2 R 5 , or R 3 and R 4 together with the carbon to which they are attached form C 3 -C 12 cycloalkyl, the process comprising:
(a) reacting a nitroalkane compound of formula IV
wherein R and R 1 are independently H, C 1 -C 6 alkyl, or C 3 -C 12 cycloalkyl, or R and R 1 together with the carbon to which they are attached form C 3 -C 12 cycloalkyl, with a molar excess of a carbonyl compound of formula III
in the presence of a basic catalyst to form an intermediate product mixture comprising free carbonyl compound of formula III and a nitroalcohol compound of formula II
(b) hydrogenating the intermediate product mixture in the presence of hydrogen and a hydrogenation catalyst such that the nitroalcohol compound of formula II and the free carbonyl compound of formula III react therein to form the tertiary aminoalcohol compound of formula I.
2. The process of claim 1 wherein the intermediate product mixture of step (a) comprises at least two moles of free carbonyl compound of formula III per mole of nitroalcohol compound of formula II.
3. The process of claim 1 wherein additional carbonyl compound of formula III is added following step (b).
4. The process of claim 1 wherein R 3 and R 4 are each independently C 1 -C 3 alkyl.
5. The process of claim 1 wherein R 3 and R 4 are each —C(OH)R 2 R 5 .
6. The process of claim 1 wherein R 3 is —C(OH)R 2 R 5 and R 4 is C 1 -C 6 alkyl.
7. The process of claim 1 wherein R 3 and R 4 together with the carbon to which they are attached form C 3 -C 12 cycloalkyl.
8. The process of claim 1 wherein R 2 and R 5 are H.
9. The process of claim 1 wherein following step (b), the concentration of the tertiary aminoalcohol compound of formula I in the intermediate product mixture is at least 0.5 percent by weight.
10. The process of claim 1 wherein the compound of formula I is 2-(dimethylamino)-2-methyl-1-propanol, N,N dimethyltris(hydroxymethyl)aminomethane, 2-(dimethylamino)-2-ethylpropane-1,3-diol, 2-(dimethylamino)-2-methylpropane-1,3-diol or 1-(dimethylamino)cyclohexylmethanol.