Formaldehyde → (S)-4-Methyl-2-[methyl-(tetrahydro-pyran-4-yl)-amino]-pentanoic acid

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Reaction Steps

A mixture of (S)-4-methyl-2-(tetrahydro-pyran-4-ylamino)-pentanoic acid (9.09 g, 42.3 mmol, Example 18, Step A) and aqueous HCHO (10 mL of 37.2%, 3.72 g, 124 mmol) was agitated in an atmosphere of hydrogen (pressure, 47-52 psi) at 50° C. in absolute ethanol (250 mL) in the presence of Pd/C (20%, 1 g) until the absorption of hydrogen almost ceased. The catalyst was removed by filtration. The filtrate was concentrated in vacuo to dryness. Fifty milliliter of water was added and concentrated to dryness, and this operation was repeated twice to remove most of HCHO. Absolute ethanol (50 mL) was then added and concentrated to dryness to remove residual water. The white solid collected was triturated with acetone. Filtration and drying under vacuum gave 8.93 g (92%) of the desired product as a white solid; mp 185-190° C. (decomposed). APCI-MS m/z 230.2 (MH+).

Provenance & Evidence