(R)-1-Phenylpropylamine → (R)-chroman-2-carboxylic acid

Participants

Reaction Steps

To a solution of Intermediate-1 (18.6 g, 104 mmol) in acetonitrile (91 mL), (R)-(+)-1-phenylpropylamine (9.14 g, 67.9 mmol) in methyl tert butyl ether (MTBE) (12 mL) solution was added in dropwise manner. After about half of the total amount of the (R)-(+)-1-phenylpropylamine solution was added. The reaction mixture was seeded with few crystals of ((R)-(+)-1-phenyl propyl ammonium (R)-(−)-chromane-2-carboxylate). The resultant thick slurry was diluted with MTBE (80 mL) and the mixture was further stirred for 6 h at RT. The salt was filtered, washed with MTBE and dried. The salt (13.7 g) was suspended in MTBE (80 mL) further aqueous HCl solution (1:1) (88 mL) was added and the mixture was stirred in cooling to 0° C. The aqueous layer was extracted with methyl tert-butyl ether (70 mL×2). The extracts were combined with organic layer and the solution was washed with 1:1 HCl solution (40 mL). The organic layer was dried over Na2SO4 and evaporated under reduced pressure to afford the title compound as a white crystalline solid (6.5 g); m/z-178.02.

Provenance & Evidence