1,2-Dichloroethane → HCID 66987881, compound

HRID 333407Notes

Reaction equation

HRID 333407 reaction equation
C([C@:18]([NH2:31])([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)[C:19]([OH:21])=O)(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[C:47]1([C:53]2([C:59](=[O:63])[CH2:60][CH2:61][CH3:62])[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.C(=O)([O-])O.[Na+]>ClCCl.C(N(CC)CC)C.CN(C)C=O>[NH2:31][C@@H:18]([CH2:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)[C:19]([N:56]1[CH2:57][CH2:58][C:53]([C:59](=[O:63])[CH2:60][CH2:61][CH3:62])([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:54][CH2:55]1)=[O:21]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 30149101-(4-Phenylpiperidin-4-yl)butan-1-one hydrochlorideHCID 66988467(S)-2-Fmoc-amino-3-(4-methoxy-phenyl)propionic acid

Product 1

HCID 66987881HCID 66987881, compoundYield 44.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution containing 11.9 g (28.5 mmol) of (S)-2-Fmoc-amino-3-(4-methoxy-phenyl)propionic acid dissolved in 120 mL of dichloromethane and 10 mL of dimethylformamide are added 5.51 g (38.9 mmol) of EDC and 5.25 g (38.9 mmol) of HOBt. After stirring for 30 minutes at room temperature, a solution of 6.95 g (26.1 mmol) of 1-(4-phenylpiperidin-4-yl)-butan-1-one hydrochloride and 18 mL of triethylamine in 150 mL of dichloromethane is added. The reaction medium is stirred for 2 hours, and saturated aqueous sodium hydrogen carbonate solution is then added. The organic compounds are extracted with dichloromethane. The organic phase is dried over magnesium sulfate and then filtered, and the solvents are evaporated off. The crude product is chromatographed on silica gel (eluent: 9/1 dichloromethane/methanol). 4.7 g of 1-{1-[(S)-2-amino-3-(4-methoxyphenyl)-propionyl]-4-phenylpiperidin-4-yl}butan-1-one in the form of an orange oil are obtained in a yield of 44%.

Workup

  1. stirringThe reaction medium is stirred for 2 hours
  2. extractionThe organic compounds are extracted with dichloromethane
  3. dry with materialThe organic phase is dried over magnesium sulfate
  4. filtrationfiltered
  5. customthe solvents are evaporated off
  6. customThe crude product is chromatographed on silica gel (eluent: 9/1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-48a247cd79834bdc8bd6a791ceca3591
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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