Methyl Acetate → (3S,5S)-3,5-Dimethyl-3-((S)-2-methyl-propane-2-sulfinylamino)-heptanoic Acid Methyl Ester

Temperature

0 °C

To a solution of diisopropylamine (3.1 mL, 22.2 mmol) in THF (40 mL) at −78° C. was slowly added butyllithium (14.4 mL, 1.6 M, 23 mmol). The mixture was stirred at 0° C. for 25 minutes and subsequently cooled down to −78° C. Methyl acetate (1.76 mL, 22.2 mmol) in THF (7 mL) was added. After Stirring for 20 minutes, chlorotitaniumtriisopropoxide (11 mL, 46.2 mmol) in THF (10 mL) was added and the resulting mixture was stirred at −78° C. for 20 minutes. (S)-2-Methyl-propane-2-sulfinic acid ((3S)-1,3-dimethyl-pentylidene)-amide (1.9 g, 8.9 mmol) in THF (10 mL) was added. The mixture was stirred at −78° C. overnight. The reaction was quenched by NH4Cl solution (50 mL). The mixture was filtered. The filtrate was extracted by EtOAc (3×70 mL). The EtOAc phase was reduced under reduce pressure and the residue was purified by a silica gel column (Hexane/EtOAc 1:1) to give the titled compound (1.61 g, 62% yield) as a colorless oil: 1H NMR (CDCl3) δ 3.64 (s, 3H), 2.60 (m, 2H), 1.47 (m, 2H), 1.44 (m, 1H), 1.36 (s, 3H), 1.27 (m, 2H), 1.19 (s, 9H), 0.90 (d, J=6.4 Hz, 3H), 0.81 (t, J=7.6 Hz, 3H); MS (APCI) (M+1)+ 292.2.

1. customat −78° C.
2. temperaturesubsequently cooled down to −78° C
3. stirringAfter Stirring for 20 minutes
4. stirringthe resulting mixture was stirred at −78° C. for 20 minutes
5. stirringThe mixture was stirred at −78° C. overnight
6. customThe reaction was quenched by NH4Cl solution (50 mL)
7. filtrationThe mixture was filtered
8. extractionThe filtrate was extracted by EtOAc (3×70 mL)
9. customthe residue was purified by a silica gel column (Hexane/EtOAc 1:1)

ORD record

ord-50a7e6c507864185bdf951432eba6337

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07388023B2