1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86692009, compound

HRID 340631Notes

Reaction equation

HRID 340631 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:14][C:15]1([F:21])[CH2:17][CH:16]1[C:18](O)=[O:19].CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>CN(C=O)C.C(O)C.CCCCCCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:18]([CH:16]3[CH2:17][C:15]3([F:21])[F:14])=[O:19])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27356291-(4-Bromophenyl)piperazineHCID 27828232,2-Difluorocyclopropane-1-carboxylic acid

Product 1

HCID 86692009HCID 86692009, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8900HeptaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(4-bromophenyl)piperazine (2.53 g, 10.5 mmol) in DMF (10 mL) was added 2,2-difluorocyclopropanecarboxylic acid (1.92 g, 15.7 mmol) 1H-benzotriazol-1-ol (2.84 g, 21.0 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide (3.26 g, 21.0 mmol) and DIEA (7.31 mL, 42.0 mmol). The resulting mixture was stirred at 50° C. for 1 h. The reaction mixture was then quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and concentrated in vacuo. Purification by chromatography on silica gel (0 to 75% EtOAc in hexanes, then 75 to 100% EtOAc in hexanes) provided the racemic compound. The racemate was then dissolved in 10% ethanol in heptane and the enantiomers were separated on an OD chiral column by eluting column with 30% ethanol in heptane. The first eluting peak was defined as enantiomer A and the second eluting peak was defined as enantiomer B. LCMS m/z 346.8 [M+H]+; 1H NMR (500 MHz, CD2Cl2) δ 7.37 (d, J=9.0 Hz, 2 H),6.80 (d, J=9.0 Hz, 2 H), 4.00-3.93 (m, 1 H),3.84-3.61 (m, 3 H),3.31-3.02 (m, 4 H),2.60-2.50 (m, 1 H),2.23-2.11 (m, 1 H),1.75-1.64 (m, 1 H).

Workup

  1. customThe reaction mixture was then quenched with saturated ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated in vacuo
  4. customPurification by chromatography on silica gel (0 to 75% EtOAc in hexanes
  5. custom75 to 100% EtOAc in hexanes) provided the racemic compound
  6. customthe enantiomers were separated on an OD chiral column
  7. washby eluting column with 30% ethanol in heptane

Sources & evidence

ORD record
ord-b0ee99ca52a14c3397a245bbd1b807a5
Source dataset
uspto-grants-2014_11
Patent number
US08895583B2

Reaction notes

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