Isopropanol → (R)-N-methyl-3-hydroxy-3-phenylpropylamine hemioxalate salt

A solution of (R)-3-iodo-1-phenylpropanol (5.0 g, 19 mmol) and catalytic amount of sodium iodide in tetrahydrofuran (20 mL) and 40% aqueous methylamine (40 mL) was stirred at room temperature for 5 hours. The reaction mixture was evaporated to 15 mL and the pH of the solution was adjusted to pH>12 via the addition of aqueous NaOH solution. The mixture was then twice extracted with toluene and the combined extracts were washed with brine. The toluene layer was evaporated to dryness and the residue dissolved in toluene (25 mL) and isopropanol (25 mL) and oxalic acid dihydrate (1.2 g, 9.5 mmol) was added and the mixture was stirred at room temperature for 2 hours. The resulting suspension was filtered and rinsed with toluene/isopropanol to give 3.0 g of (R)—N-methyl-3-hydroxy-3-phenylpropylamine hemioxalate salt as an off-white solid. The solid (2.9 g) was free based with sodium hydroxide solution and extracted with toluene. The extracts were washed with brine and then evaporated to dryness to give 2.2 g of (R)—N-methyl-3-hydroxy-3-phenylpropylamine as an off-white solid [α]D23=36° (c 1, CHCl3).

1. customThe reaction mixture was evaporated to 15 mL
2. additionthe pH of the solution was adjusted to pH>12 via the addition of aqueous NaOH solution
3. extractionThe mixture was then twice extracted with toluene
4. washthe combined extracts were washed with brine
5. customThe toluene layer was evaporated to dryness
6. dissolutionthe residue dissolved in toluene (25 mL)
7. filtrationThe resulting suspension was filtered
8. washrinsed with toluene/isopropanol

ORD record

ord-b6515616323c4f9cb2b2d34ac49876be

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07485754B2