4-Methylmorpholine → Z-Gly-Leu-PheCH2F

HRID 2225910

Reaction equation

HRID 2225910 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[CH2:7][CH:8]([CH3:10])[CH3:9])=[O:4].N(C(OCC1C=CC=CC=1)=O)CC(O)=O.[OH-].[Na+].CN1CCOCC1.[NH2:48][C@H:49]([C:57]([CH2:59][F:60])=[O:58])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.Cl>C1COCC1.CN(C=O)C>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:2][C:3]([NH:5][C@H:6]([C:11]([NH:48][C@H:49]([C:57]([CH2:59][F:60])=[O:58])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:13])[CH2:7][CH:8]([CH3:9])[CH3:10])=[O:4]

Participants

8

Reactant 5

HCID 79724-Methylmorpholine2×HCID 14349BenzyloxycarbonylglycineHCID 14798Sodium HydroxideHCID 96816Z-Gly-Leu-OH2×HCID 131717227PheCH2F hydrochloride

Product 1

HCID 131717229Z-Gly-Leu-PheCH2FYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Z-Gly-LeuOH was made by mixed anhydride coupling of Z-GlyOH and LeuOBzl tosylate, followed by NaOH hydrolysis of the benzyl ester. To a solution of Z-Gly-LeuOH (0.223 g, 0.69 mmol) in THF (4 mL) at -20° C. was added NMM (76 uL, 0.69 mmol), followed by IBCF (90 uL, 0.69 mmol). After 10 minutes, a precooled solution of PheCH2F hydrochloride (0.15 g, 0.69 mmol) in DMF (1 mL) was added, followed by a second equivalent (76 uL, 0.69 mmol) of NMM. After 30 minutes of stirring, the mixture was quenched with 1M HCl (5 mL), extracted with ethyl acetate (20 mL), washed with saturated aqueous NaHCO3 (6 mL), brine (5 mL), dried over MgSO4, filtered, and evaporated to dryness. The residue was crystallized from ether/hexane to give 0.18 g (54%) of Z-Gly-Leu-PheCH2F.

Workup

  1. customthe mixture was quenched with 1M HCl (5 mL)
  2. extractionextracted with ethyl acetate (20 mL)
  3. washwashed with saturated aqueous NaHCO3 (6 mL), brine (5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was crystallized from ether/hexane

Sources & evidence

ORD record
ord-26bc2a0e74524daa87dc4a944c426604
Source dataset
uspto-grants-1994_09
Patent number
US05344939

Linked notes

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