3-((S)-1-DiMethylaMino-ethyl)phenol hydrochloride synthesis

Yield:894079-56-2 80%

Reaction Conditions:

Stage #1: 3-[(S)-1-(methylamino)ethyl]phenol;formaldehyd;formic acid for 3 h;Heating / reflux;
Stage #2: with hydrogenchloride in formic acid;water at 20; for 0.5 h;

Steps:

1

[33] (S)-3-(l-monomethylaminoethyl)phenol (Formula 7, 29.2 g, 0.192 mol, 99.6% ee) EPO was added to a mixture of 85% formic acid (66 ml, 0.153 mol) and formaldehyde (28.7 ml, 0.385 mol). The reaction mixture was refluxed for 3 hours, cooled to room temperature. The remaining formic acid was concentrated. Water (60 ml) and cone. HCl (20 ml) were added to the concentrate, stirred for 30 minutes, and washed with ether (150 ml). The obtained aqueous layer was concentrated, and then acetone (150 ml) was added thereto to precipitate crystals. The crystals were filtered, and dried to afford (S)-3-(l-dimethylaminoethyl)phenol hydrochloride (hydrochloride salt of the compound of Formula 8, 31. Ig, 80%).[34] The analytical results of the compound of Formula 7 are as follows.[35] ' H-NMR (CDCl ): 7.19 (IH, m), 6.77 (3H, m), 3.63 (IH, q), 2.33 (3H, s), 1.39(3H, d)[36] ¹³ C-NMR (CDCl ): 157.3, 145.5, 129.7, 118.9, 115.0, 113.2, 60.0, 33.9, 22.5[37] [α ]_D ²⁰ = -68.0 (c = 5.0 in pyridine)[38] HPLC analysis[39] Column: Shiseido chiral CD-Ph 4.6 x 250 mm, 5 μm[40] Flow rate: 0.7 ml/min.[41] Wavelength: 200 nm[42] Solvent: 0.025M NaH₂PO₄ solution (MeOHZH₂O = 1.5/1)[43] Retention time:[44] 14 min.: (S)-3-(l-monomethylaminoethyl)phenol hydrochloride[45] 22 min.: (R)-3-(l-monomethylaminoethyl)phenol hydrochloride[46] The analytical results of the chloride of Compound 8 are as follows.[47] ¹³C-NMR (D₂O): 156.9, 136.7, 131.5, 121.3, 117.7, 116.3, 66.7, 41.0, 16.0[48] ¹H-NMR (D₂O): 7.43 (IH, m), 7.27 (3H, m), 4.44 (IH, q), 2.81 (6H, s), 1.72 (3H, d)

References:

WO2006/68386,2006,A1 Location in patent:Page/Page column 4-5