Hydrochloric Acid → (S)-5-(3-(2-((((9H-fluoren-9-yl)methoxy) carbonyl)amino)-3-oxo-3-(piperidin-1-yl)propyl)phenyl)pentanoic acid

HRID 1482253Notes

Reaction equation

HRID 1482253 reaction equation
C(OC([NH:8][C@H:9]([C:28](=[O:35])[N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)[CH2:10][C:11]1[CH:12]=[C:13]([CH2:17][CH2:18][CH2:19]CC(OC(C)(C)C)=O)[CH:14]=[CH:15][CH:16]=1)=O)(C)(C)C.F[C:37](F)(F)[C:38]([OH:40])=[O:39].C(=O)([O-])[O-].[Na+].[Na+].[CH:49]1[C:61]2[CH:60]([CH2:62][O:63][C:64]([O:66]N3C(=O)CCC3=O)=O)[C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:53]=2[CH:52]=[CH:51][CH:50]=1.Cl>C(Cl)Cl>[CH:58]1[C:59]2[CH:60]([CH2:62][O:63][C:64]([NH:8][C@H:9]([C:28](=[O:35])[N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)[CH2:10][C:11]3[CH:12]=[C:13]([CH2:17][CH2:18][CH2:19][CH2:37][C:38]([OH:40])=[O:39])[CH:14]=[CH:15][CH:16]=3)=[O:66])[C:61]3[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:54]=2[CH:55]=[CH:56][CH:57]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 89668522tert-butyl (S)-5-(3-(2-((tert-butoxycarbonyl)amino)-3-oxo-3-(piperidin-1-yl)propyl)phenyl)pentanoate

Product 1

HCID 89668700(S)-5-(3-(2-((((9H-fluoren-9-yl)methoxy) carbonyl)amino)-3-oxo-3-(piperidin-1-yl)propyl)phenyl)pentanoic acidYield 89.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (S)-5-(3-(2-((tert-butoxycarbonyl)amino)-3-oxo-3-(piperidin-1-yl)propyl)phenyl)pentanoate (Compound SP431) (4.70 g, 9.62 mmol) was dissolved in DCM (30.0 ml), trifluoroacetic acid (15.0 ml, 195 mmol) was added and the mixture was stirred for 50 minutes at room temperature, after which the reaction solution was concentrated under reduced pressure. The resulting residue was dissolved in dioxane (34 ml) and a 10% aqueous sodium carbonate solution (68 ml), N-(9-fluorenylmethoxycarbonyloxy)-succinimide (3.15 g, 9.33 mmol) was added and the mixture was stirred at room temperature for 3 hours. The reaction solution was made acidic by adding a 5 N aqueous HCl solution and then extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous Na2SO4, and then filtered and concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-30:70) to afford the title compound (Compound SP432) (4.65 g, 87%).

Workup

  1. concentrationafter which the reaction solution was concentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in dioxane (34 ml)
  3. stirringthe mixture was stirred at room temperature for 3 hours
  4. extractionextracted with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-30:70)

Sources & evidence

ORD record
ord-fb990001edb14a3db9c5b83e9a535e71
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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