Hydrochloric Acid → (2S,4R)-N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid 2-ethyl ester

L-cysteine hydrochloride monohydrate (50 g, 285 mmol) was dissolved in water (100 ml), and the pH of the solution was adjusted to 5.15 with 6N aqueous sodium hydroxide. The reaction mixture was heated to 40° C., ethyl pyruvate (38 ml, 342 mmol) was gradually added thereto, and the mixture was stirred at 40° C. for 4 hr. Water was added, and the mixture was cooled to room temperature to precipitate the crystals and the crystals were collected by filtration. The obtained crystals were washed with water, and dried under reduced pressure at 50° C. to give 2-methylthiazolidine-2,4-dicarboxylic acid 2-ethyl ester (trans form:cis form=88:12, 12.1 g, yield 19%). The synthesized 2-methylthiazolidine-2,4-dicarboxylic acid 2-ethyl ester (5 g, 22.8 mmol) was dissolved in ethyl acetate (40 ml), and triethylamine (6.4 ml, 45.9 mmol) was added under argon. Acetyl chloride (2.4 ml, 33.8 mmol) was slowly added dropwise, and the mixture was stirred at room temperature overnight. After completion of the reaction, water (15 ml) was added thereto, and the pH of the mixture was adjusted to 1.0 with HCl. The aqueous layer was separated, and the organic layer was washed with water (10 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate. The obtained ethyl acetate solution was concentrated to precipitate crystals. The crystals were collected by filtration, washed with heptane/ethyl acetate=1/1 (10 ml), and dried under reduced pressure at 50° C. to give (2S,4R)-N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid 2-ethyl ester as crystals (3.3 g, yield 55%).

1. additionwas added
2. customThe aqueous layer was separated
3. washthe organic layer was washed with water (10 ml)
4. washwashed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationThe obtained ethyl acetate solution was concentrated
7. customto precipitate crystals
8. filtrationThe crystals were collected by filtration
9. washwashed with heptane/ethyl acetate=1/1 (10 ml)
10. customdried under reduced pressure at 50° C.

ORDレコード

ord-b3bd5720a33b4d3abaa0d82cefc6c444

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09308157B2