ChemicalBook CAS DataBase List (S)-1-CBZ-2-METHYL-PIPERIDIN-4-ONE

(S)-1-CBZ-2-METHYL-PIPERIDIN-4-ONE synthesis

6synthesis methods

Product Name:(S)-1-CBZ-2-METHYL-PIPERIDIN-4-ONE
CAS Number:921599-74-8
Molecular formula:C14H17NO3
Molecular Weight:247.29

849928-34-3
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$36.00/250mg

921599-74-8
25 suppliers
$125.00/100mg

Yield:921599-74-8 96%

Reaction Conditions:

with Chiralpak AD in methanol;

Steps:

1.3

Step 3. Isolation of benzyl (2S)-2-methyl-4-oxopiperidine-1 -carboxylate (C3). Racemic benzyl 2-methyl-4-oxopiperidine-1-carboxylate (C2) (4.01 kg, 16.2 mol) was dissolved in methanol (80 L) and separated into its enantiomers via chromatography (six Chiralpak AD columns, each 5 cm x 10 cm, 20 μηη, 40 °C; Eluant: methanol; Feed rate 7.2 mL/minute; Eluant rate: 225 mL/minute). The first-eluting enantiomer was the desired (2S) enantiomer, obtained as an amber oil. Yield of benzyl (2S)-2-methyl-4- oxopiperidine-1 -carboxylate (C3): 1 .932 kg, 7.813 mol, 96% with respect to available desired enantiomer. Chiral purity via HPLC analysis: 99.5:0.5 (Column: Chiralpak AD-H, 4.6 mm x 150 mm, 5 μηη; Eluant: 0.1 % trifluoroacetic acid in methanol). {Note: in a similar chiral separation carried out on a different batch of racemic material, conversion to the dimethyl ketal benzyl 4,4-dimethoxy-2-methylpiperidine-1 -carboxylate was observed. This was attributed to slight acidity in the starting material and column packing. A different chiral separation was therefore developed to avoid the presence of alcohol (Column: Chiralpak IA, 20 μηη; Eluant: 60/40 heptane/propan-2-yl acetate). Using six 1 cm x 10 cm columns, a sample of benzyl 2-methyl-4-oxopiperidine-1 -carboxylate (C2) (2.96 g) provided benzyl (2S)-2-methyl-4-oxopiperidine-1-carboxylate (C3) in a 99.5:0.5 ratio with its enantiomer (Chiral purity was assessed via HPLC analysis;Column: Chiralpak IA, 4.6 mm x 250 mm, 5 μηη; Eluant: 60/40 heptane/propan-2-yl acetate). The desired (2S) enantiomer was the first-eluting enantiomer.}

References:

WO2012/172449,2012,A1 Location in patent:Page/Page column 25-26