2,2-Dimethyl-3-pentanone → HCID 15196530, compound

NH2 --(R)--CH(Et)CMe3 : To a cooled solution (0°) of 4,4-dimethyl-3-pentanone (106 g, 0.92 mmol) and (R)-α-methylbenzylamine (111 g, 0.92 mmol) in benzene (1 L), a solution of TiCl4 (50.5 mL, 0.46 mmol) in benzene (200 mL) was added at a rate that kept the temperature of the mixture below 10°. Thereafter, the mixture was stirred mechanically for 3 h at 40°, cooled to room temperature and filtered through diatomaceous earth. The diatomaceous earth was washed with Et2O. The combined filtrate and wash was concentrated. The residue was dissolved in dry MeOH (2 L). The solution was cooled to 0° and NaBH4 (20 g, 0.53 mmol) was added portionwise while maintaining the temperature of the mixture below 5°. The methanol was evaporated. The residue was dissolved in Et2O. The solution was washed with brine, dried (MgSO4) and evaporated to dryness to give a reddish oil (a 18:1 mixture of diastereoisomers as indicated by NMR). The oil was purified by flash chromatography (SiO2, eluent: EtOAc/hexane, 7:93) to afford N-(1(R)-phenylethyl)-1(R)-ethyl-2,2-dimethylpropyl-amine as a liquid (110 g, 54%). This material was dissolved in hexane (1.5 L). 6N HCl in dioxane (90 mL) was added to the solution over a period of 15 min. The resulting white solid was collected on a filter and then washed with hexane to provide N-(1(R)-phenyl-ethyl)-1(R)-ethyl-2,2-dimethylpropylamine hydrochloride (125 g, 97%). 1H NMR(CDCl3) δ 0.55 (t, J=7.5 Hz, 3H), 1.14 (s, 9H), 1.54-1.95 (m, 2H), 2.23 (d, J=6.5 Hz, 3H), 2.36-2.44 (m, 1H), 4.31-4.49 (m, 1H), 7.30-7.48 (m, 3H), 7.74-7.79 (m, 2H).

1. customthe temperature of the mixture below 10°
2. filtrationfiltered through diatomaceous earth
3. washThe diatomaceous earth was washed with Et2O
4. washThe combined filtrate and wash
5. concentrationwas concentrated
6. dissolutionThe residue was dissolved in dry MeOH (2 L)
7. temperatureThe solution was cooled to 0°
8. temperaturewhile maintaining the temperature of the mixture below 5°
9. customThe methanol was evaporated
10. dissolutionThe residue was dissolved in Et2O
11. washThe solution was washed with brine
12. dry with materialdried (MgSO4)
13. customevaporated to dryness
14. customto give a reddish oil (
15. additiona 18:1 mixture of diastereoisomers
16. customThe oil was purified by flash chromatography (SiO2, eluent: EtOAc/hexane, 7:93)

ORD record

ord-65e0d934bb874f0daad95271ce756864

Source dataset

uspto-grants-1996_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05574015