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

HRID 1379588Notes

Reaction equation

HRID 1379588 reaction equation
[CH3:1][C:2]([CH3:8])([CH3:7])[C:3](=O)[CH2:4][CH3:5].[CH3:9][C@@H:10]([NH2:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[BH4-].[Na+]>C1C=CC=CC=1.Cl[Ti](Cl)(Cl)Cl>[C:11]1([C@H:10]([NH:17][C@H:3]([CH2:4][CH3:5])[C:2]([CH3:8])([CH3:7])[CH3:1])[CH3:9])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 1363632,2-Dimethyl-3-pentanoneHCID 6431891-Phenethylamine, (+)-HCID 4311764Sodium borohydride

Product 1

HCID 15196530HCID 15196530, compoundYield 54.7%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 241BenzeneSolvent2×

Procedure

To a cooled solution (0°) of 4,4-dimethyl-3-pentanone (106 g, 0.928 mol) and (R)-α-methylbenzylamine (111 g, 0.916 mol) in benzene (1 L), a solution of TiCl4 (50.5 mL, 0.461 mol) 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 (20°-22°) 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 mol) 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 concentrated 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-dimethylpropylamine as a liquid (110 g, 54% yield). This material was dissolved in hexane (1.5 L). 1N HCl in E2O (550 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)-phenylethyl)-1(R)-ethyl-2,2-dimethylpropylamine hydrochloride (125 g, 97% yield). 1H NMR(CDCl3) δ7.79-7.74 (m, 2H), 7.48-7.30 (m, 3H), 4.49-4.31 (m, 1H), 2.44-2.36 (m, 1H), 2.23 (d, J=6.5 Hz, 3H), 1.95-1.54 (m, 2H), 1.14 (s, 9H), 0.55 (t, J=7.5 Hz, 3H).

Workup

  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. concentrationconcentrated
  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)

Sources & evidence

ORD record
ord-fa1faae34dc5463695246ca8af75331a
Source dataset
uspto-grants-1997_09
Patent number
US05672586

Reaction notes

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