4-Isopropylaniline → 4-tert-Butoxycarbonylamino-4-(4-isopropyl-phenylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

HRID 1949082Notes

Reaction equation

HRID 1949082 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([C:17](O)=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:28]([C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1)([CH3:30])[CH3:29].CCN=C=NCCCN(C)C.C(OCC)(=O)C>CN(C1C=CN=CC=1)C.C1COCC1.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][C:14]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([C:17](=[O:18])[NH:35][C:34]2[CH:36]=[CH:37][C:31]([CH:28]([CH3:30])[CH3:29])=[CH:32][CH:33]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 74644-IsopropylanilineHCID 8857Ethyl AcetateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 231027164-n-Boc-amino-1-cbz-isonipecotic acid

Product 1

HCID 669213864-tert-Butoxycarbonylamino-4-(4-isopropyl-phenylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3.78 g (10 mmol) 4-tert-Butoxycarbonylamino-piperidine-1,4-dicarboxylic acid monobenzyl ester (commercially available), 1.76 g (13 mmol) 4-isopropyl-aniline (commercially available), 2.1 g (11 mmol) EDCI and 1.36 g (11 mmol) DMAP in 50 mL THF was stirred at room temperature over night. After concentration of the mixture ethyl acetate and water was added. The mixture was extracted with ethyl acetate and the combined organic fractions were dried with MgSO4 and evaporated. The residue was purified over silica eluting with a gradient formed from ethyl acetate and hexane to afford after evaporation of the product containing fractions 2.85 g (57%) of the title compound as white solid. MS (m/e): 496.3 [(M+H)+].

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. dry with materialthe combined organic fractions were dried with MgSO4
  3. customevaporated
  4. customThe residue was purified over silica eluting with a gradient
  5. customformed from ethyl acetate and hexane
  6. customto afford
  7. customafter evaporation of the product
  8. additioncontaining fractions 2.85 g (57%) of the title compound as white solid

Sources & evidence

ORD record
ord-ec3e62697e3a4449a59a3795194673f9
Source dataset
uspto-grants-2013_03
Patent number
US08399676B2

Reaction notes

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