4-Methylmorpholine → 2-((2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionylamino)-3-oxo-3-phenylpropionic acid methylester

HRID 849883

Reaction equation

HRID 849883 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[CH3:39][O:40][C:41](=[O:52])[CH:42]([NH2:51])[C:43](=[O:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1>[CH3:39][O:40][C:41](=[O:52])[CH:42]([NH:51][C:10](=[O:11])[C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=1)[C:43](=[O:50])[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 2734481(2R)-2-(((tert-butoxy)carbonyl)amino)-3-(naphthalen-2-yl)propanoic acidHCID 132906482-Amino-3-oxo-3-phenylpropionic acid methylester

Product 1

HCID 543050742-((2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionylamino)-3-oxo-3-phenylpropionic acid methylesterYield 72.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

(2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionic acid (5.49 g; 17.42 mmol) was dissolved in dry tetrahydrofuran (200 ml) and N-methylmorpholine (1.92 ml; 17.42 mmol) was added. The reaction mixture was cooled to -20° C. and stirred 15 min. Isobutyl chloroformate (2.27 ml; 17.42 mmol) was dissolved in dry tetrahydrofuran (3 ml) and added dropwise to the reaction mixture at -20° C. N-methylmorpholine (1.92 ml; 17.42 mmol) and 2-amino-3-oxo-3-phenylpropionic acid methylester (4.0 g; 17.42 mmol) were added and and the mixture was stirred 30 min at -20° C. The reaction mixture was heated to room temperature and the solvent was removed in vacuo. The residue was dissolved in methylene chloride (200 ml), washed with water (200 ml) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (5×45 cm) using heptane/ethyl acetate/methylene chloride (2:1:1) as eluent to afford 6.19 g of a diastereomeric mixture of 2-((2R)-2-tert-butoxycarbonylamino-3-(2-naphthyl)propionylamino)-3-oxo-3-phenylpropionic acid methylester.

Workup

  1. additionadded dropwise to the reaction mixture at -20° C
  2. stirringthe mixture was stirred 30 min at -20° C
  3. temperatureThe reaction mixture was heated to room temperature
  4. customthe solvent was removed in vacuo
  5. dissolutionThe residue was dissolved in methylene chloride (200 ml)
  6. washwashed with water (200 ml)
  7. dry with materialdried (magnesium sulfate)
  8. customThe solvent was removed in vacuo
  9. customthe residue was chromatographed on silica (5×45 cm)

Sources & evidence

ORD record
ord-1493aa39239c45f88b189767790982d5
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Linked notes

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