Iodine → Methyl 3-[(2,2-dimethylbutanoyl)thio]propanoate

Temperatur

25 °C

A solution of N,N-diisopropylethylamine (19.9 mL, 120 mmol) and methyl 3-mercaptopropanoate (7.21 60 mmol) in isopropyl acetate (i-PrOAc, 100 mL) was cooled to an internal temperature of 2° C. To this vigorously stirred solution, 2,2-dimethylbutanoyl chloride (8.1 g, 60 mmol) was added dropwise over 10 min. The resulting suspension was stirred at 25° C. for 2 h. The reaction was monitored by checking the disappearance of methyl 3-mercaptopropanoate using thin-layer chromatography (TLC) on silica plates. Spots were stained with iodine (eluent: 5% EtOAc/heptane; Rf of methyl 3-mercaptopropanoate: 0.20). The reaction was quenched by addition of saturated ammonium chloride (100 mL) followed by i-PrOAc (100 mL) and the resultant mixture stirred until all solid dissolved. The phases were separated and the organic phase was washed successively with 1% aqueous hydrochloric acid (100 mL) and then water (2×50 mL). The organic phase was then dried over sodium sulfate, filtered, and concentrated under reduced pressure (45° C. bath, 50 mm Hg) to obtain a crude mixture as a pale yellow liquid. The crude mixture is subjected to column chromatography over silica gel using a heptane to 2% EtOAc:heptane gradient. Fractions comprising the pure product were combined and concentrated to afford 10.5 g (80%) of methyl 3-(2,2-dimethylbutanoylthio)propionate (DMB-S-MMP).

1. customThe reaction was quenched by addition of saturated ammonium chloride (100 mL)
2. stirringthe resultant mixture stirred until all solid
3. dissolutiondissolved
4. customThe phases were separated
5. washthe organic phase was washed successively with 1% aqueous hydrochloric acid (100 mL)
6. dry with materialThe organic phase was then dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure (45° C. bath, 50 mm Hg)
9. customto obtain a crude mixture as a pale yellow liquid
10. concentrationconcentrated

ORD-Eintrag

ord-7c4f7b182d5e4ab296f1b1c6403b2e70

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09181570B2