4-(9H-FLUOREN-9-YLMETHOXYCARBONYLAMINO)-PIPERIDINE-1,4-DICARBOXYLIC ACID MONO-TERT-BUTYL ESTER

4-(((9H-fluoren-9-yl)methoxy)carbonylamino)-1-(tert- butoxycarbonyl)piperidine-4-carboxylic acid (Scheme 1, compound 8) [0225] A solution of 4-amino-1 -(terf-butoxycarbonyl)piperidine-4- carboxylic acid (5 g, 20.5 mmol) in THF (300 mL) and NaIn a dry 25-mL, two-necked, round-bottomed flask was charged with coupling reagent (1.0 equiv) in DCM (1 mL/mmol) and treated under stirring with DIEA (3.0 equiv) at 0 C. for 5 min. A solution of 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-1-(tert- butoxycarbonyl)piperidine-4-carboxylic acid (130 mg, 0.28 mmol) in DCM (3mL) was treated with 1-chloro-N, N, 2-trimethylprop-1-en-1-amine (74 muL, 0.56 mmol). After 1 h, 2-chloro-3-methylaniline (79 mg, 0.56 mmol) in pyridine (1 mL) was added. After stirring overnight, the reaction mixture was partitioned between DCM and 1 M aqueous solution of HCl (5 mL each). The phases were passed through phase sep cartridge and the solvent was removed under vacuum. The crude products were purified by chromatography (EA/isohexane) to afford 144 mg (87%) of Intermediate 11A. LCMS [m/z] calculated for C33H36ClN3O5: 589.2; found 612.0 [M+Na]+, tR=3.04 min (Method 4).

Cyclic ?,?-disubstituted amino acid for the preparation of water-soluble highly helical peptides.

Molecular Weight:466.5
XLogP3:3.9
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:7
Exact Mass:466.21038668
Monoisotopic Mass:466.21038668
Topological Polar Surface Area:105
Heavy Atom Count:34
Complexity:748
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes