4-Methoxybenzaldehyde → (2R)-1-[(4-Methoxybenzyl)amino]-2-propanol

HRID 51301

Reaction equation

HRID 51301 reaction equation
[NH2:1][CH2:2][C@H:3]([OH:5])[CH3:4].[CH:6](=O)[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.C(O)(=O)C>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][NH:1][CH2:2][C@H:3]([OH:5])[CH3:4])=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 312444-MethoxybenzaldehydeHCID 439938(2R)-1-aminopropan-2-olHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 40761789(2R)-1-[(4-Methoxybenzyl)amino]-2-propanolYield 62.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (R)-(−)-1-amino-2-propanol (9.00 g, 0.12 mol) in tetrahydrofuran (40 ml) and acetic acid (5 ml) was added dropwise to a solution of p-anisaldehyde (5.45 g, 0.04 mol) in tetrahydrofuran (40 ml), and once addition was complete, the solution was stirred at room temperature for 2 hours. The solution was cooled in an ice-bath, and sodium triacetoxyborohydride (9.50 g, 0.0.045 mol) was added portionwise, and then the mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between dichloromethane (150 ml) and sodium hydroxide solution (150 ml, 0.5N). The layers were separated and the aqueous phase was saturated with sodium chloride, then extracted with further dichloromethane (3×30 ml). The combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (gradient elution 98:2:0.2 to 97:3:0.3 dichloromethane:methanol:0.88 NH3) to afford an orange oil (4.9 g). 1H-NMR (CDCl3, 400 MHz) δ: 1.12 (d, 3H), 2.39 (dd, 1H), 2.70 (dd, 1H), 3.62-3.79 (m, 6H), 6.82 (d, 2H), 7.19 (d, 2H). LRMS: m/z (ES+) 196 [MH+].

Workup

  1. temperatureThe solution was cooled in an ice-bath
  2. stirringthe mixture was stirred at room temperature for 18 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue was partitioned between dichloromethane (150 ml) and sodium hydroxide solution (150 ml, 0.5N)
  5. customThe layers were separated
  6. extractionextracted with further dichloromethane (3×30 ml)
  7. dry with materialThe combined organic solutions were dried (MgSO4)
  8. customevaporated under reduced pressure
  9. customThe residue was purified by chromatography on silica gel (gradient elution 98:2:0.2 to 97:3:0.3 dichloromethane:methanol:0.88 NH3)

Sources & evidence

ORD record
ord-74c8f6b4c9fc4a698743832bc6f1b3db
Source dataset
uspto-grants-2004_03
Patent number
US06713496B2

Linked notes

Loading…