Formaldehyde → HCID 53312153, compound

Participants

Reaction Conditions

Reaction Steps

The mixture of (R/S)-3-Benzoyl-(S)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethyl-pyrrolidin-2-one (4a, R1=pyrrolidinylmethyl, R4=phenyl) (0.44 g, 1 mmol), formaldehyde (37% in water, 0.24 g, 3 mmol), TBAH (6.5 mg, 0.01 mmol) and K2CO3 (0.28 g, 1.3 mmol, dissolved in 1 mL water) in 5 mL dry tetrahydrofuran was heated to 50° C. and stirred for 2 hours. Then the reaction mixture is diluted with 5 mL brine and stirred for 15 min, stop stirring, and remove the lower aqueous layer. the organic phase is then concentrated in vacuo. ethyl acetate 10 mL is added, filtered and the filtrate concentrated and purified by column chromatography eluting with 5:1 heptane/ethyl acetate to afford (R)-5-Biphenyl-4-ylmethyl-3-methylene-1-pyrrolidin-1-ylmethyl-pyrrolidin-2-one (1a, R1=pyrrolidinylmethyl). 1HNMR (400 MHz, CDCl3): 1.68 (m, 4H, 2×CH2CH2), 2.06 (m, 1H, 3-CHH), 2.31 (m, 1H, 3-CHH), 2.51 (m, 4H, 2×NCH2), 2.67 (d, 1H, 5-CHH), 2.65 (dd, 1H, N—CHH), 3.15 (dd, 1H, N—CHH), 2.92 (d, 1H, 5-CHH), 4.01 (m, 1H, 4-CH), 5.54 (d, 1H, ═CHH), 6.02 (d, 1H, ═CHH), 7.20-7.80 (14H, m, aromatic).

Provenance & Evidence