4-Methylmorpholine → 3-[(N-Boc-Piperidin-4-ylmethyl)aminocarbonyl]benzoyl-2(S)-3-pyridylsulfonylamino-beta-alanyl-glycine benzyl ester

HRID 265905Notes

Reaction equation

HRID 265905 reaction equation
CO[C:3](=[O:42])[C@@H:4]([NH:32][S:33]([C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1)(=[O:35])=[O:34])[CH2:5][NH:6][C:7](=[O:31])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[O:15])[CH:9]=1.O[Li].O.[CH2:46]([O:53][C:54](=[O:57])[CH2:55][NH2:56])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.Cl.CN1CCOCC1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C.C1COCC1.CO.O>[CH2:46]([O:53][C:54](=[O:57])[CH2:55][NH:56][C:3](=[O:42])[C@@H:4]([NH:32][S:33]([C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1)(=[O:34])=[O:35])[CH2:5][NH:6][C:7](=[O:31])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:20][CH2:19]2)=[O:15])[CH:9]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 168937Lithium hydroxide, monohydrateHCID 11701227Benzyl 2-aminoacetate hydrochlorideHCID 867510973-[(N-Boc-Piperidin-4-ylmethyl)aminocarbonyl]benzoyl-2(S)-3-pyridylsulfonylamino-beta-alanine methyl ester

Product 1

HCID 867510963-[(N-Boc-Piperidin-4-ylmethyl)aminocarbonyl]benzoyl-2(S)-3-pyridylsulfonylamino-beta-alanyl-glycine benzyl ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A solution of 31-1 (0.75 g, 1.5 mmol) in 1:1:1 THF/MeOH/H2O (15 mL) was treated with LiOH·H2O (0.37 g, 8.8 mmol). After 45 min. the solution was concentrated, diluted with water, washed with EtOAc. The aqueous layer was acidified to pH 2-3 with 10% KHSO4 and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and evaporated to give an acid which was dissolved in acetonitrile (3 mL) and treated with glycine benzyl ester·HCl (0.1 g, 0.5 mmol), N-methylmorpholine (0.11 mL, 0.98 mmol), and BOP reagent (0.26 g, 0.58 mmol) for 24 h. The solution was concentrated, dissolved in water and EtOAc and the layers separated. The organic layer was dried (Na2SO4), filtered and evaporated. Column chromatography (SiO2, 70% acetone/hexanes) gave 31-2 as a white solid.

Workup

  1. concentrationAfter 45 min. the solution was concentrated
  2. additiondiluted with water
  3. washwashed with EtOAc
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto give an acid which
  9. concentrationThe solution was concentrated
  10. dissolutiondissolved in water
  11. customEtOAc and the layers separated
  12. dry with materialThe organic layer was dried (Na2SO4)
  13. filtrationfiltered
  14. customevaporated

Sources & evidence

ORD record
ord-7e9ed2f007cb48f0bc00c794dc4226d5
Source dataset
uspto-grants-1997_07
Patent number
US05648368

Reaction notes

Loading…