Citric Acid → HCID 178426697, compound

HRID 1443398Notes

Reaction equation

HRID 1443398 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][C:14]1[C:19]([CH3:20])=[CH:18][C:17]([C:21](=[O:23])[NH2:22])=[CH:16][C:15]=1[CH3:24])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.[C:35]1([C:41]2[N:42]=[C:43]([CH:46]3[CH2:51][CH2:50][CH2:49][CH2:48][NH:47]3)[NH:44][CH:45]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.CN(C)CCCCN=C=NCC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH2:13][C:14]1[C:19]([CH3:20])=[CH:18][C:17]([C:21](=[O:23])[NH2:22])=[CH:16][C:15]=1[CH3:24])[C:10](=[O:11])[N:47]1[CH2:48][CH2:49][CH2:50][CH2:51][CH:46]1[C:43]1[NH:44][CH:45]=[C:41]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:42]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 757711-HydroxybenzotriazoleHCID 21914090(4-Dimethylamino-butyl)-ethyl-carbodiimideHCID 221476672-((Tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoic acidHCID 178420113HCID 178420113, compound

Product 1

HCID 178426697HCID 178426697, compoundYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-tert-Butoxycarbonylamino-3-(4-carbamoyl-2,6-dimethyl-phenyl)-propionic acid (0.42 g, 1.25 mmol) was dissolved in DMF (5 mL) followed by 1-hydroxybenzotriazole (0.34 g, 1.75 mmol), and the resulting solution was cooled to 0° C. To this reaction mixture was added 2-(4-phenyl-1H-imidazol-2-yl)-piperidine (0.31 g, 1.75 mmol) followed by (4-dimethylamino-butyl)-ethyl-carbodiimide (0.34 g, 1.75 mmol). The reaction was then warmed to room temperature and stirred for 16 hours. The reaction mixture was then combined with 2N citric acid and washed multiple times with ethyl acetate. The combined organics were washed with saturated aqueous NaHCO3, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield 600 mg of desired product {1-(4-carbamoyl-2,6-dimethyl-benzyl)-2-oxo-2-[2-(4-phenyl-1H-imidazol-2-yl)-piperidin-1-yl]-ethyl}-carbamic acid tert-butyl ester as a glass which was used as is without further purification. (TLC: 5:1 CHCl3: MeOH Rf=0.6)

Workup

  1. temperatureThe reaction was then warmed to room temperature
  2. washwashed multiple times with ethyl acetate
  3. washThe combined organics were washed with saturated aqueous NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-555cb85cb11e4a3a88994cf9ab704ffc
Source dataset
uspto-grants-2010_02
Patent number
US07659402B2

Reaction notes

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