4-Isopropylaniline → 4-(4-Isopropyl-phenylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 2381163Notes

Reaction equation

HRID 2381163 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.[CH:35]([C:38]1[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=1)([CH3:37])[CH3:36]>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:16])[NH:44][C:41]2[CH:42]=[CH:43][C:38]([CH:35]([CH3:37])[CH3:36])=[CH:39][CH:40]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 74644-IsopropylanilineHCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 292052294-(4-Isopropyl-phenylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl esterYield 48.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (2.293 g) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (1.84 g) in acetonitrile (50 ml) were treated under ice cooling and an argon atmosphere with N-methyl-morpholine (3.034 g) and the mixture was stirred for 2 h at 0° C. Then 4-isopropyl-phenylamine (1.42 g) in acetonitrile was added dropwise and the reaction mixture was stirred at RT for 48 h. The reaction mixture was partitioned between ethyl acetate and aqueous 1M HCl, the layers were separated and the aqueous layer washed with 2M aqueous KHCO3 then dried over Na2SO4. The solvent was evaporated off. The residue was then triturated with AcOEt/diethyl ether/heptane to give the desired 4-(4-isopropyl-phenylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (1.68 g) as white solid. MS (ESI): 347.28 (MH+)

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and aqueous 1M HCl
  2. customthe layers were separated
  3. washthe aqueous layer washed with 2M aqueous KHCO3
  4. dry with materialthen dried over Na2SO4
  5. customThe solvent was evaporated off
  6. customThe residue was then triturated with AcOEt/diethyl ether/heptane

Sources & evidence

ORD record
ord-f5360d48b434420ca41e957c3bc31f33
Source dataset
uspto-grants-2012_09
Patent number
US08258158B2

Reaction notes

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