Pyridine → HCID 57956922, compound

HRID 553074Notes

Reaction equation

HRID 553074 reaction equation
C(O[C:9](=[O:37])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[C:15](=[O:36])[CH2:16][CH2:17][C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30]C(C)(C)C)=O)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)C1C=CC=CC=1.F[C:39](F)(F)[C:40](O)=O.N1C=[CH:49][CH:48]=[CH:47][CH:46]=1.[C:51](Cl)(=[O:58])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>C(Cl)Cl>[CH2:51]([O:58][C:9](=[O:37])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[C:15](=[O:36])[CH2:16][CH2:17][C:18](=[O:35])[C@@H:19]([NH:27][C:28](=[O:30])[C:40]1[CH:39]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 7412Benzoyl chlorideHCID 57956925HCID 57956925, compound

Product 1

HCID 57956922HCID 57956922, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of benzyl ester compound 10 (100 mg, 0.1968 mmol, 1.0 eq.) was dissolved in dry CH2Cl2 (10 mL) and cooled in an ice-water bath. 0.5M solution Trifluoroacetic acid (3.0 mL) was added dropwise and the resulting mixture stirred for 1 h. The mixture was allowed to warm-up to room temperature and stirred for a further 1 h. The resulting mixture was wash sequentially with 10% NaHCO3 (10 mL), H2O (10 mL), brine (10 mL) and dried the organic extract was dried over anhydrous MgSO4 and evaporation of the solvent afforded a crude. To the crude mixture was added pyridine (5.0 mL) and cooled in an ice-water bath and then benzoyl chloride (0.1 mL, 0.862 mmol) was added. The mixture was stirred for 1 h at this temperature and a further 24 h at room temperature. The yellow solution was evaporated and then purified by column chromatography on silica gel elution with 50% EtOAc-hexane afforded (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-proline benzyl ester as a pale yellow viscous oil which foams in 85% yield. 1H NMR was identical. Hydrogenolysis of this benzyl ester with 10% Pd/C (50 mg) and dry EtOAc-MeOH (3:1 ratio) (10 mL) for 48 h afforded the compound 5a in 90% yield. 1H NMR was identical as previously reported.

Workup

  1. temperaturecooled in an ice-water bath
  2. stirringstirred for a further 1 h
  3. washThe resulting mixture was wash sequentially with 10% NaHCO3 (10 mL), H2O (10 mL), brine (10 mL)
  4. customdried the
  5. extractionorganic extract
  6. dry with materialwas dried over anhydrous MgSO4 and evaporation of the solvent
  7. customafforded a crude
  8. temperaturecooled in an ice-water bath
  9. stirringThe mixture was stirred for 1 h at this temperature and a further 24 h at room temperature
  10. customThe yellow solution was evaporated
  11. custompurified by column chromatography on silica gel elution with 50% EtOAc-hexane

Sources & evidence

ORD record
ord-f1a8f996979246a6b47d198b5604be37
Source dataset
uspto-grants-2011_05
Patent number
US07951834B2

Reaction notes

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