Preparation and application of 1-amino-2-propanol_Industrial additives

Background and overview^[1]

1-Amino-2-propanol (MIPA) is an important fine chemical raw material with a wide range of uses. It is commonly used as surfactants, metal working fluids, paints and coatings, textile printing and dyeing, personal care products, water treatment agents, One of the raw materials for pharmaceutical and pesticide intermediates.

Preparation^[1-2]

Report 1,

Put propylene oxide and ammonia with a concentration of 95wt% into the mixer at a molar ratio of 1:1.0 respectively using a metering pump to control the temperature in the mixer to 0°C and the pressure to 3.0MPa; continuously pass the mixed liquid through After entering the microchannel reactor, the material reacts in the channel of the reaction section of the reactor at a temperature of 60°C and a pressure of 3.0MPa. After staying for 0.1S, it enters the cooling section of the microchannel reactor and rapidly cools down to terminate the reaction. The outlet temperature is 0 ℃, the residence time is 2S, and the specific cooling rate is controlled at about 1800-2000℃/min. The low boiling matter is then removed through a stripping tower to obtain the product 1-amino-2-propanol with a content of 99.2%. In this embodiment, the microchannel reactor is specifically made of stainless steel, where the inner diameter of the microchannel is 0.05mm and the length of the microchannel is 0.8m.

Report 2,

A preparation method of (S)-1-amino-2-propanol, specifically including the following steps:

(1) Dissolve sodium tert-butoxide (230g, 2.39mol) in tetrahydrofuran (2L), slowly add trifluoroacetamide (226g, 2mol) under ice bath, stir for 30 minutes; then add ( S)-propylene oxide (128g, 2.2mol), naturally warmed to room temperature, continued stirring for 10h, and then stirred and reacted at 35°C for another 2h; after the reaction, a total of 1L of 2N (equivalent concentration) hydrochloric acid was added dropwise to the system for neutralization. , then add 1L of water, let stand and separate the layers, extract the aqueous phase with dichloromethane, combine the organic phases, dry over anhydrous sodium sulfate, and concentrate under reduced pressure to obtain a total of 318g of intermediate product I, with a yield of 93%. ¹H-NMR of intermediate product I (CDCl₃, MHz): δ1.08(d,3H),3.37(m,2H),4.0(m,1H) ),7.12(brs,1H).

(2) Dissolve the intermediate product I (310g, 1.81mol) obtained in step (1) in methanol (1.5L), add 200mL water and potassium carbonate (550g, 4mol), stir at room temperature for 6h, filter and concentrate To dryness, the obtained product was dissolved in dichloromethane, filtered to remove insoluble matter, dried over anhydrous sodium sulfate, concentrated, and distilled under reduced pressure to obtain a total of 122g of the target product (S)-1-amino-2-propanol, yield is 90%.

¹H-NMR (CDCl₃, MHz): δ1.15(d,3H),2.43(dd,1H),2.64(dd,1H) ,3.53-3.64(m,1H),3.77(brs,3H).

Report 3,

A preparation method of (R)-1-amino-2-propanol, specifically including the following steps:

(1) Dissolve sodium tert-butoxide (300g, 3.12mol) in tetrahydrofuran (2L), slowly add trifluoroacetamide (294g, 2.6mol) under ice bath, stir for 30 minutes; then add under ice bath (R)-propylene oxide (166g, 2.96mol), naturally warmed to room temperature, continued to stir for 10h, and then stirred for 2h at 35°C; after the reaction, a total of 1.3L of 2N (equivalent concentration) hydrochloric acid was added dropwise to the system. Neutralize, then add 1.3 L of water, let stand to separate layers, extract the aqueous phase with methylene chloride, combine the organic phases, dry over anhydrous sodium sulfate, and concentrate under reduced pressure to obtain a total of 423 g of intermediate product I, with a yield of 95%.

¹H-NMR of intermediate product I (CDCl₃, MHz): δ1.07(d,3H),3.36(m,2H),3.99( m,1H),7.11(brs,1H).

(2) Dissolve the intermediate product I (420g, 2.45mol) obtained in step (1) in methanol (2L), add 350mL water and potassium carbonate (744g, 5.4mol), stir at room temperature for 6h, filter and concentrate To dryness, the obtained product was dissolved in dichloromethane, filtered to remove insoluble matter, dried over anhydrous sodium sulfate, concentrated, and distilled under reduced pressure to obtain a total of 171g of the target product (R)-1-amino-2-propanol, yield is 93%.

¹H-NMR (CDCl₃, MHz): δ1.17(d,3H),2.45(dd,1H),2.66(dd,1H) ,3.54-3.67(m,1H),3.76(brs,3H).

Apply^[3]

CN201310281153.3 discloses a new synthesis process of tenofovir disoproxil, using (R)-(-)-1-amino-2-propanol as raw material and diethyl p-toluenesulfonyloxymethylphosphate After the reaction, (R)-2-O-[bis(isopropoxycarbonyloxymethyl)phosphono-methyl]-1-amino-2-propanol (IV) is obtained by hydrolysis and condensation. The compound of formula (IV) is condensed with 5-amino-4,6-dichloropyrimidine, and then tenofovir disoproxil is prepared through ring closure and aminolysis. The invention provides a new tenofovir disoproxil synthesis process, which has low production cost, safe process, good product quality, and is suitable for industrial production.

References

[1] [Chinese invention] CN20181077.3 A preparation method of 1-amino-2-propanol

[2] [Chinese invention] CN202010535582.9 Preparation method of chiral 1-amino-2-propanol

[3] CN201310281153.3 New synthesis process of tenofovir disoproxil