# US 10,246,400 B2 · Method for the preparation of (S)-2-acetyloxypropionic acid and derivatives thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,246,400 B2
- Document ID: US10246400B2
- Status: Granted
- Kind: B2
- Application number: 15/946,204
- Filed: 2018-04-05
- Published: 2018-08-09
- Granted: 2019-04-02
- Earliest claimed: 2014-06-10
- Assignees: Bracco Imaging S.P.A.
- Applicants: Bracco Imaging S.P.A.
- Inventors: Roberta Fretta; Pietro Delogu; Fernanda Di Giorgio; Alfonso Nardelli; Stefano Sguassero; Carlo Felice Viscardi
- Web page: https://patentgrep.com/patent/US10246400B2

## CPC

- C07C 67/08: by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
- B01D 3/009: {in combination with chemical reactions}
- C07C 51/44: by distillation
- C07C 67/287: by introduction of halogen; by substitution of halogen atoms by other halogen atoms
- C07C 67/54: by distillation
- C07B 2200/07: Optical isomers
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention relates to a method for the acetylation of an aqueous solution of lactic acid to (S)-2-acetyloxypropionic acid. The process comprises in particular removing water from the solution of lactic acid and reacting lactic acid with acetic anhydride in the presence of acetic acid.

## Claims

### Claim 1

A method for preparing an (S)-2-acetyloxypropionic acid in a preparation assembly comprising a distillation section (A) and a reaction section (B), the distillation section (A) comprising a top portion and a bottom portion connected to said reaction section (B), the method comprising the steps of:
a. continuously feeding an aqueous solution of a lactic acid to the top portion of the distillation section (A);
b. feeding an acetic anhydride into the reaction section (B);
c. reacting the lactic acid with the acetic anhydride in the reaction section (B), thus forming the (S)-2-acetyloxypropionic acid and an acetic acid;
d. evaporating a vapor mixture of the acetic acid and of the unreacted acetic anhydride from the reaction section (B);
e. feeding the vapor mixture of step d to the distillation section (A) for stripping water from the aqueous solution of lactic acid to form a substantially anhydrous lactic acid which counterflows through said distillation section (A) towards the reaction section (B), so that a mixture of the substantially anhydrous lactic acid and the acetic acid enters the reaction section (B) from the bottom portion of the distillation section (A);
f. recovering the (S)-2-acetyloxypropionic acid from the reaction section (B); and
g. collecting a diluted aqueous solution of the acetic acid at the top portion of the distillation section (A).

### Claim 2 (depends on 1)

The method according to claim 1, wherein the reaction section (B) of the preparation assembly comprises two separate sub-sections (B′) and (B″), wherein the sub-section (B′) is dedicated to performing an acetylation reaction between the lactic acid and the acetic anhydride, and sub-section (B″) is dedicated to evaporation and feeding of the acetic acid and the unreacted acetic anhydride to the distillation section (A).

### Claim 3 (depends on 1)

The method according to claim 1, wherein the preparation assembly is under a negative pressure.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the negative pressure is between 5 mbar and 200 mbar.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the aqueous solution of the lactic acid has a concentration from 20% to 90% (w/w) of lactic acid.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the molar ratio between the acetic anhydride and the lactic acid in step c is from 1.01 to 1.5.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the vapor mixture of step d is fed continuously to the distillation section (A).

### Claim 8 (depends on 1)

The method according to claim 1, wherein the reaction section (B) comprises at least two stirred jacketed reactor tanks.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the reaction section (B) comprises at least three stirred jacketed reactor tanks.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the lactic acid is reacted with the acetic anhydride in the presence of a solid acidic catalyst.

### Claim 11 (depends on 1)

The method according to claim 1, further comprising the step of reacting the (S)-2-acetyloxypropionic acid with a thionyl chloride to give a (S)-2-acetyloxypropionyl chloride.

### Claim 12 (depends on 2)

The method according to claim 2, wherein the aqueous solution of the lactic acid has a concentration from 20% to 90% (w/w) of lactic acid.

### Claim 13 (depends on 2)

The method according to claim 2, wherein the reaction section (B) comprises at least a first tank and a second tank, wherein: (i) the first tank, which is continuously fed with the acetic anhydride and with a mixture of the lactic acid and the acetic acid from the distillation section (A), performs the acetylation reaction; and (ii) the second tank is dedicated to the evaporation of the vapor mixture of the acetic acid and the unreacted acetic anhydride from a completed reaction mixture, the vapor mixture being continuously fed to the distillation section (A).

### Claim 14 (depends on 2)

The method according to claim 2, wherein the reaction section (B) comprises at least a first tank, a second tank, and a third tank, wherein: (i) the first tank, which has been previously fed with the acetic anhydride and with a mixture of the lactic acid and the acetic acid from the distillation section (A), is dedicated to performing the acetylation reaction in a batch mode; (ii) the second tank is dedicated to the evaporation of the vapor mixture of the acetic acid and the unreacted acetic anhydride from a completed reaction mixture, the vapor mixture being continuously fed to the distillation section (A); and (iii) the third tank is dedicated to collecting a mixture of the lactic acid and the acetic acid continuously flowing from the distillation section (A).

### Claim 15 (depends on 12)

The method according to claim 12, wherein the reaction section (B) comprises at least a first tank, a second tank, and a third tank, wherein: (i) the first tank, which has been previously fed with the acetic anhydride and with a mixture of the lactic acid and the acetic acid from the distillation section (A), is dedicated to performing the acetylation reaction in a batch mode; (ii) the second tank is dedicated to the evaporation of the vapor mixture of the acetic acid and the unreacted acetic anhydride from a completed reaction mixture, the vapor mixture being continuously fed to the distillation section (A); and (iii) the third tank is dedicated to collecting a mixture of the lactic acid and the acetic acid continuously flowing from the distillation section (A).

### Claim 16 (depends on 14)

The method according to claim 14, wherein the first tank, the second tank, and the third tank are interchangeable with one another.

### Claim 17 (depends on 15)

The method according to claim 15, wherein the first tank, the second tank, and the third tank are interchangeable with one another.

### Claim 18 (depends on 15)

The method according to claim 15, wherein the molar ratio between the acetic anhydride and the lactic acid in step c is from 1.01 to 1.5.