Triethylamine → HCID 178523839, compound

HRID 2244134Notes

Reaction equation

HRID 2244134 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]([C:12]([OH:14])=O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.C1CCC(N=C=NC2CCCCC2)CC1.[NH2:47][C@H:48]1[CH2:53][CH2:52][N:51]([C:54]([C:56]2[CH:61]=[C:60]([C:62]([F:65])([F:64])[F:63])[CH:59]=[C:58]([C:66]([F:69])([F:68])[F:67])[CH:57]=2)=[O:55])[C@H:50]([CH2:70][C:71]2[CH:76]=[CH:75][C:74]([Cl:77])=[CH:73][CH:72]=2)[CH2:49]1>C(Cl)Cl.C1COCC1>[F:69][C:66]([F:67])([F:68])[C:58]1[CH:57]=[C:56]([CH:61]=[C:60]([C:62]([F:63])([F:64])[F:65])[CH:59]=1)[C:54]([N:51]1[CH2:52][CH2:53][C@H:48]([NH:47][C:12]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=[C:2]([OH:1])[CH:11]=2)=[O:14])[CH2:49][C@H:50]1[CH2:70][C:71]1[CH:72]=[CH:73][C:74]([Cl:77])=[CH:75][CH:76]=1)=[O:55]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 22869970HCID 22869970, compoundHCID 178524625HCID 178524625, compound

Product 1

HCID 178523839HCID 178523839, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred mixture of 2.52 g (13.32 mMol) 2-hydroxyquinoline-4-carboxylic acid, 2.7 g (15.98 mMol) HOBt (80%), 3.7 ml (26.64 mMol) triethylamine and 3.8 g (18.64 mMol) DCC in 50 ml of CH2Cl2 were added at room temperature 12.3 g (13.32 mMol) [(2R,4S)-4-Amino-2-(4-chloro-benzyl)-piperidin-1-yl]-(3,5-bis-trifluoromethyl-phenyl)-methanone (synthesis described in EP 707006A). After 18 h the reaction mixture was diluted with 500 ml THF and filtered through a fritted glass funnel with suction. The filtrate was further diluted with ethyl acetate and washed three times with brine. The organic phase was dried with Na2SO4 and concentrated in vacuo. The product was purified by chromatography on silica gel using successively EtOAc/CH2Cl2 (2:1), EtOAc and EtOAc/THF (3:1) as eluents. The product was suspended in hexane and stirred at 60° C. overnight. The mixture was filtered and dried and a yield of 6.2 g of white crystals. M.p.222-224° C.

Workup

  1. filtrationfiltered through a fritted glass funnel with suction
  2. additionThe filtrate was further diluted with ethyl acetate
  3. washwashed three times with brine
  4. dry with materialThe organic phase was dried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe product was purified by chromatography on silica gel using successively EtOAc/CH2Cl2 (2:1), EtOAc and EtOAc/THF (3:1) as eluents
  7. filtrationThe mixture was filtered
  8. customdried

Sources & evidence

ORD record
ord-85b82a2e4d5345aaaa1eef0e99fa5b41
Source dataset
uspto-grants-2010_03
Patent number
US07678814B2

Reaction notes

Loading…