4-(METHOXYMETHYL)PIPERIDINE synthesis

Yield:-

Reaction Conditions:

Stage #1:1-tert-Butyloxycarbonyl-4-methoxymethyl-piperidine with trifluoroacetic acid in dichloromethane
Stage #2: with sodium hydroxide in dichloromethane;water

Steps:

3.218 3.218 3-[3-(4-Methoxymethyl-piperidine-1-yl)-propyl]-3H-benzothiazol-2-one(61KS89-oxalate)
3.218 3-[3-(4-Methoxymethyl-piperidine-1-yl)-propyl]-3H-benzothiazol-2-one(61KS89-oxalate) To a solution of 1-tert-butyloxycarbonyl-4-methoxymethyl-piperidine (61KS83) (0.088 g, 0.385 mmol) in DCM (2 mL) was added TFA (2 mL) under stirring. After complete conversion of the starting material the mixture was basified (2M NaOH) and extracted with DCM. After drying (Na₂SO₄) of the combined organic phase, filtering and concentration, the crude product was reacted with 3-(3-iodopropyl)-3H-benzothiazol-2-one (61KS80) (0.147 g, 0.462 mmol) and K₂CO₃ (0.106 g, 0.770 mmol) to give the title compound (61KS89) (0.086 g, 67%). The oxalate salt was prepared by dissolving the product in Et₂O and a minimum of MeOH followed by the addition of a solution of oxalic acid (1.1 eq of obtained product) in Et₂O. Filtration gave the title compound (61KS89-oxalate). NMR of the free base was recorded. ¹H NMR (CDCl₃) δ 1.23 (dq, 2H, J=3.9 Hz, 12.1 Hz), 1.48-1.63 (m, 1H), 1.64-1.73 (m, 2H), 1.83-1.95 (m, 4H), 2.35 (t, 2H, J=6.9 Hz), 2.84 (m, 2H, J=11.8 Hz), 3.19 (d, 2H, J=7.2 Hz, -C₂OCH₃), 3.30 (s, 3H, -CH₂OCH₃), 3.97 (t, 2H, J=7.2 Hz, N(from Ar)-C₂CH₂CH₂), 7.07-7.40 (m, 4H, Ar); ¹³C NMR (CDCl₃): δ 25.3, 29.5, 36.4, 41.3, 53.7, 55.7, 59.0, 78.2 (-H₂OCH₃), 111.0, 122.7, 123.0, 123.1, 126.4, 137.6, 170.1 (C=O); HPLC-MS (ammonium acetate): [M+H]⁺=321.36

References:

Kelly, Nicholas Michael;Koch, Kristian Norup;Tolf, Bo-Ragnar US2004/67931, 2004, A1 Location in patent:Page/Page column 36