Cyclohexylamine → [3-(4-Cyclohexylcarbamoyl-piperidin-1-ylmethyl)-phenyl]-carbamic acid tert-butyl ester

A suspension of crude 1-(3-tert-butoxycarbonylamino-benzyl)-piperidine-4-carboxylic acid (6.7 g, 20 mmol) in DCM (250 mL) and DMF (0.2 mL) is treated with oxalyl chloride (25 mmol, 2.21 mL) dropwise at 0° C. during 20 min. under nitrogen. The reaction mixture is stirred at RT for 2 h. Then the solvent is evaporated under reduced pressure and dried under high vacuum. The crude acid chloride is dissolved in DCM (250 mL) and treated with DIPEA (20 mmol, 3.42 mL) and cooled down to 0° C. A solution of cyclohexylamine (2.18 g, 22 mmol) in DCM (20 mL) is added dropwise over 15 min. and the resulting mixture is stirred for 2 h. at RT. The reaction mixture is washed twice with aq. sat. NaHCO3 (100 mL) and dried over MgSO4. After evaporation of the solvent, the crude residue is purified by flash chromatography on silica gel using a mixture of DCM/MeOH 9:1. After concentration of the product containing fractions, the title compound (2.44 g, 29%) is obtained as a beige powder: LC-MS A: tR=0.66 min; [M+H]+=416.2.

1. customThen the solvent is evaporated under reduced pressure
2. customdried under high vacuum
3. dissolutionThe crude acid chloride is dissolved in DCM (250 mL)
4. temperaturecooled down to 0° C
5. stirringthe resulting mixture is stirred for 2 h. at RT
6. washThe reaction mixture is washed twice with aq. sat. NaHCO3 (100 mL)
7. dry with materialdried over MgSO4
8. customAfter evaporation of the solvent
9. customthe crude residue is purified by flash chromatography on silica gel using
10. additiona mixture of DCM/MeOH 9:1
11. additionAfter concentration of the product containing fractions

ORD-Eintrag

ord-224fd679768749c6b68316bb8170ca4d

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09428456B2