Acetyl chloride → ((S)-1-Dimethoxymethyl-2-methyl-propyl)-methyl-amine hydrochloride

Temperature

15 °C

5.0 g Crude Boc-N-methyl-valinal (23.2 mmol) were dissolved in 40 ml methanol and cooled to ˜15° C. A solution of 3.3 ml (46.4 mmol) acetyl chloride in 10 ml methanol was added all at once and the yellowish solution was stirred at RT for 1 h (gas evolution). 22.2 g Trimethyl orthoformate (209 mmol) were now added and the reaction mixture was stirred at RT over night (18 h). The solvent and the excess of the orthoester were removed by rotary evaporation (40° C./≧10 mbar) and the resulting beige, crystalline residue (4.6 g) was dissolved in ca. 45 ml isopropyl acetate at ˜70° C. After cooling to RT and crystallization at −20° C. for 17 h the crystal suspension was filtered and dried (50° C./10 mbar/16 h) affording 3.2 g (69%) product as greenish needles, [α]D=40.3 (CHCl3; c=1). 1H-NMR:

1. stirringthe reaction mixture was stirred at RT over night (18 h)
2. customThe solvent and the excess of the orthoester were removed by rotary evaporation (40° C./≧10 mbar)
3. dissolutionthe resulting beige, crystalline residue (4.6 g) was dissolved in ca. 45 ml isopropyl acetate at ˜70° C
4. temperatureAfter cooling to RT
5. customcrystallization at −20° C. for 17 h the crystal suspension
6. filtrationwas filtered
7. customdried (50° C./10 mbar/16 h)

ORD record

ord-ba35abf739874e2981067ef84bfd8edd

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07312343B2