HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

4-Methylmorpholine → 1-[2-(4-Fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethylcarbamoyl]-piperidine-4-carboxylic acid tert-butyl ester

HRID 419751
Notes
Print preview

Reaction equation

HRID 419751 reaction equation
CN1CCOCC1.C(O[C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=[O:22])[CH2:17][CH2:16]1)=[O:14])(C)(C)C.ClC(O[CH2:28][CH:29]([CH3:31])[CH3:30])=O.Cl.[NH2:33][CH2:34][C:35]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([C:44]([F:47])([F:46])[F:45])[CH:38]=1)=[O:36]>C1COCC1>[C:29]([O:23][C:21]([CH:18]1[CH2:17][CH2:16][N:15]([C:13](=[O:14])[NH:33][CH2:34][C:35]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[C:39]([C:44]([F:47])([F:45])[F:46])[CH:38]=2)=[O:36])[CH2:20][CH2:19]1)=[O:22])([CH3:31])([CH3:30])[CH3:28]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 666499872-Amino-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone Hydrochloride

Product 1

HCID 666498871-[2-(4-Fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethylcarbamoyl]-piperidine-4-carboxylic acid tert-butyl ester
Yield 70.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Add N-methylmorpholine (3 equiv; 631.52 mmoles; 69.66 mL) to a solution of Piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (1.20 equiv; 252.61 mmoles; 57.92 g) in THF (400 mL). Cool the mixture to −10° C. with a dry ice-acetone bath. Add isobutyl chloroformate (1.1 equiv; 231.56 mmoles; 30.26 mL) dropwise while maintaining the temperature below −5° C. After 30 min at −5°−10° C., add 2-amino-1-(4-fluoro-3-trifluoromethyl-phenyl)-ethanone hydrochloride (54.23 g; 1.00 equiv; 210.51 mmoles) suspended in THF (300 mL) and stir the mixture in the bath at −5° C. for 20 min. Stir for 1 hour at room temperature. Add water and EtOAc, then wash the organic layer with water and saturated aqueous sodium chloride. Dry over MgSO4, filter and remove solvent in vacuo. Suspend the crude in MTBE and stir for 2 hours. Filter the solid and dry in vacuo to give 1-[2-(4-Fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethylcarbamoyl]-piperidine-4-carboxylic acid tert-butyl ester (64.44 g; 70.79% yield).

Workup

  1. stirringStir for 1 hour at room temperature
  2. washAdd water and EtOAc, then wash the organic layer with water and saturated aqueous sodium chloride
  3. dry with materialDry over MgSO4
  4. filtrationfilter
  5. customremove solvent in vacuo
  6. stirringstir for 2 hours
  7. filtrationFilter the solid
  8. customdry in vacuo

Sources & evidence

ORD record
ord-7c77cf5da3fe4051b6fd546b1ba670a3
Source dataset
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08093383B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes