Benzene → HCID 15196530, compound

HRID 2260106Notes

Reaction equation

HRID 2260106 reaction equation
[CH3:1][C:2]([CH3:8])([CH3:7])[C:3](=O)[CH2:4][CH3:5].C([N:11]([CH2:14][CH3:15])CC)C.[BH4-].[Na+].Cl.[CH:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>Cl[Ti](Cl)(Cl)Cl>[C:19]1([C@H:14]([NH:11][C@H:3]([CH2:4][CH3:5])[C:2]([CH3:8])([CH3:7])[CH3:1])[CH3:15])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 5

HCID 241Benzene2×HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 1363632,2-Dimethyl-3-pentanoneHCID 4311764Sodium borohydride

Product 1

HCID 15196530HCID 15196530, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 24193Titanium TetrachlorideCatalyst

Procedure

NH2 --(R)--CH(C2H5)C(CH3)3 : To a cooled solution (0°) of 4,4-dimethyl-3-pentanone (106 g, 0.928 mol), triethylamine (513 mL, 3.68 mol), and (R)-δ-methylbenzylamine (114 g, 0.940 mol) in dry benzene (1 L), a solution of TiCl4 (50.5 mL, 0,459 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 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°. Approximately 2 mL of 10% aqueous HCl was added and the MeOH 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-dimethylpropylamine 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)-phenylethyl)-1(R)-ethyl-2,2-dimethylpropyl hydrochloride (125 g, 97%). 1H NMR(CDCl3) δ0.55 (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).

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 MeOH 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)

Sources & evidence

ORD record
ord-1a7414240fa64ad3869f78e36f700454
Source dataset
uspto-grants-1995_12
Patent number
US05476841

Reaction notes

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