Fmoc-D-pipecolic acid

102774-86-7

3105-95-1

101555-63-9

The general procedure for the synthesis of (R)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid from the compound (CAS: 102774-86-7) and L-2-piperidinic acid is as follows: 1. L-piperidine acid (3.6 g, 38.7 mmol) was dissolved in 40 mL of 10% sodium carbonate solution in a round-bottomed flask and stirred at room temperature for 5 min. 2. Fmoc-OSu (8.5 g, 34.8 mmol) dissolved in 35 mL of dioxane was added to the above solution and the reaction mixture was stirred overnight. 3. Upon completion of the reaction, water was added and the aqueous layer was extracted with ethyl acetate. 4. The aqueous layer was acidified to pH=2 by adding concentrated hydrochloric acid. 5. The acidified aqueous layer was extracted with ethyl acetate (3 x 40 mL). 6. 6. The organic phases were combined and washed sequentially with 1N HCl and brine, then dried with anhydrous magnesium sulfate and concentrated in vacuum to obtain a colorless oily liquid. 7. The oily liquid was dissolved in ether and cooled to give a fluffy white solid, which was washed with hexane and dried to give (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (8.2 g, 38.7 mmol, 83% yield). Product characterization data: - TLC (hexane:EtOAc:TFA = 1:1:0.2): rf = 0.60 - HPLC (gradient A) retention time = 24.6-24.8 min - 1H NMR (300 MHz, CDCl3) δ = 1.28-1.53 (m, 2H), 1.69-1.82 (m, 3H), 2.19-2.37 (m, 1H), 3.15 (t, 1H, J = 13.2 Hz), 4.05-4.33 (m, 2H), 4.37-4.49 (m, 2H), 4.76- 5.05 (m, 1H), 7.28-7.41 (m, 4H), 7.55-7.62 (m, 2H), 1.77 (s, 2H). - 13C NMR (75 MHz, CDCl3) δ = 20.72, 24.70, 26.55, 41.94, 47.25, 54.19, 67.86, 119.97, 125.08, 127.07, 127.68, 141.33, 143.89, 156.65, 177.36. - MS (ESI) m/z: 352.66 [M + H]+, calculated: 352.40 [M + H]+.