4-Methylmorpholine → 2-Tert-butoxycarbonylamino-4-(methoxy-methyl-carbamoyl)-butyric acid benzyl ester

HRID 71749Notes

Reaction equation

HRID 71749 reaction equation
CN1CCOCC1.[CH2:8]([O:15][C:16](=[O:31])[CH:17]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:18][CH2:19][C:20]([OH:22])=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CN([C:35]([O:39][N:40]1N=NC2C=CC=N[C:41]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.CNOC>CN(C)C=O>[CH2:8]([O:15][C:16](=[O:31])[CH:17]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:18][CH2:19][C:20](=[O:22])[N:40]([O:39][CH3:35])[CH3:41])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 3255276Boc-D-glutamic acid 1-benzyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 731946592-Tert-butoxycarbonylamino-4-(methoxy-methyl-carbamoyl)-butyric acid benzyl esterYield 100.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Methylmorpholine (9.77 mL, 88.9 mmol) was added to a suspension of 2-tert-butoxycarbonylamino-pentanedioic acid 1-benzyl ester (6 g, 17.7 mmol), and HATU (8.11 g, 21.3 mmol) in dimethylformamide (20 mL). After 5 minutes N,O-dimethylhydroxylamine hydrochloride (2.60 g, 26.7 mmol), was added to the solution. After 1 hour the solvent was removed under reduced pressure. The residue was taken up in ethyl acetate (150 mL), and washed with water (100 mL), aqueous hydrogen chloride (0.5 N, 2×100 mL), saturated sodium bicarbonate (100 mL), and saturated sodium chloride (100 mL). The organic phase was dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was subjected to flash chromatography with eluent of ethyl acetate and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to yield 2-tert-butoxycarbonylamino-4-(methoxy-methyl-carbamoyl)-butyric acid benzyl ester (6.8 g, 17.8 mmol, 99%). C19H28N2O6 calculated 380.2 observed [M+1]+ 381.2; rt=2.48 min.

Workup

  1. additionwas added to the solution
  2. customAfter 1 hour the solvent was removed under reduced pressure
  3. washwashed with water (100 mL), aqueous hydrogen chloride (0.5 N, 2×100 mL), saturated sodium bicarbonate (100 mL), and saturated sodium chloride (100 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-565175a6a88c41b59cdda15f18086e9b
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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