Ethyl Acetate → (αR,βS)-α-(Aminomethyl)-β-[bis(phenylmethyl)amino]benzenepropanol

HRID 1077709Notes

Reaction equation

HRID 1077709 reaction equation
[CH2:1]([N:8]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C@@H:10]([OH:13])[C:11]#[N:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].CCOC(C)=O.[OH-].[Na+]>CCOCC>[NH2:12][CH2:11][C@@H:10]([OH:13])[C@@H:9]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 11792597HCID 11792597, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 11279881(αR,βS)-α-(Aminomethyl)-β-[bis(phenylmethyl)amino]benzenepropanolYield 66%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A solution of 3(S)-(dibenzylamino)-2(R)-hydroxy-4-phenylbutanenitrile [50.82 g, 143 mmol] described by M. T. Reetz et al., Tetrahedron Lett., 29, 3295 (1988)] in anhydrous Et2O (250 mL) was added dropwise over a period of 2 h to a stirred, cooled (0°) mixture of LiAlH4 (8.10 g, 213 mmol) and anhydrous Et2O (500 mL). The mixture was allowed to warm to room temperature while being stirred for 4.5 h. The mixture was cooled again to 0°. EtOAc (100 mL) was added slowly over 15 min. Stirring was continued for 15 min at 0°. A cold (0°) solution of 2N NaOH (250 mL) was added dropwise to the reaction mixture giving a white suspension/emulsion. The cloudy organic supernatant was separated and the remainder of the suspension/emulsion was passed through a 45 μm filter. The filtrate was extracted with EtOAc and the extract was combined with the first organic phase. After drying over NaCl/Na2SO4, the solution was concentrated to a volume of ca 100 mL and allowed to stand at 5° for 18 h. The precipitated material was separated, triturated with hexane (300 mL), collected by filtration, and dried under reduced pressure to give the title compound as a white solid (34 g, 66% yield). Mp: 72°-76°. [α]D24 -1.9° (c=1, MeOH). [α]Hg36524 -24.0° (c=1, MeOH). 1H NMR (CDCl3, 400 MHz) δ 2.68 (dd, J=12.6, 7.6, 7.2 Hz, 1H), 2.81 (dd, J=12.6, 3.8, 3.5 Hz, 1H), 2.86-3.00 (m, 2H), 3.08 (dd, J=14.1, 7.6, 7.3 Hz, 1H), 3.59 (d, J=13.7 Hz, 2H), 3.69 (m, 1H), 3.71 (d, J=13.7 Hz, 2H), 7.16-7.35 (m, 15H). FAB-MS (m/z): 361 (M+H)+.

Workup

  1. temperaturecooled
  2. temperatureThe mixture was cooled again to 0°
  3. stirringStirring
  4. waitwas continued for 15 min at 0°
  5. customgiving a white suspension/emulsion
  6. customThe cloudy organic supernatant was separated
  7. filtrationfilter
  8. extractionThe filtrate was extracted with EtOAc
  9. dry with materialAfter drying over NaCl/Na2SO4
  10. concentrationthe solution was concentrated to a volume of ca 100 mL
  11. waitto stand at 5° for 18 h
  12. customThe precipitated material was separated
  13. customtriturated with hexane (300 mL)
  14. filtrationcollected by filtration
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-fdb7f62330b84797bf5fa11af5eba69a
Source dataset
uspto-grants-1996_08
Patent number
US05545640

Reaction notes

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