4-Methoxybenzaldehyde → (2R)-2-(4-Methoxybenzylamino)-4-methylpentanoic acid amide

HRID 1893830Notes

Reaction equation

HRID 1893830 reaction equation
Cl.[NH2:2][C@@H:3]([C:8]([NH2:10])=[O:9])[CH2:4][CH:5]([CH3:7])[CH3:6].[CH:11](=O)[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1.[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][NH:2][C@H:3]([CH2:4][CH:5]([CH3:7])[CH3:6])[C:8]([NH2:10])=[O:9])=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 312444-MethoxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 56776963(R)-2-Amino-4-methylpentanamide hydrochloride

Product 1

HCID 59432820(2R)-2-(4-Methoxybenzylamino)-4-methylpentanoic acid amide

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

A solution of D-leucinamide hydrochloride (2.8 g, 16.8 mmol), and p-anisaldehyde (2.29 g, 16.8 mmol) in methanol (150 mL) was treated with anhydrous ZnCl2 (538 mg, 5 mmol). The resulting suspension was then treated with NaCNBH3 (1.05 g, 16.8 mmol) portion wise and heated at reflux for 3 h. The reaction was cooled to rt, quenched with saturated NaHCO3 (3 mL), diluted with EtOAc (500 mL), and washed with brine. Concentration afforded the crude benzyl amine as a white wax, which was carried on without further purification (3.57 g, 84%). MS (ESI), (M+H)+251.4; 1H NMR (CDCl3) δ 7.20 (d, 2H, J=6.6), 7.10 (br s, 2H), 6.88 (d, 2H, J=8.4), 5.30 (br s, 1H), 3.80 (s, 3H), 3.63 (dd, 2H, J=4.5, 12), 1.44-1.65 (m, 3H), 0.95 (d, 3H, J=6.3), 0.80 (d, 3H, J=6.3).

Workup

  1. temperatureheated
  2. temperatureat reflux for 3 h
  3. customquenched with saturated NaHCO3 (3 mL)
  4. additiondiluted with EtOAc (500 mL)
  5. washwashed with brine
  6. concentrationConcentration

Sources & evidence

ORD record
ord-cb32f8544f5b46d891ed2dfb232e60a5
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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