4-Methylmorpholine → 2-[2-({[2-(4-Bromo-phenyl)-2-oxo-ethyl carbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetylamino]-3-methyl-butyric acid methyl ester

HRID 2039008Notes

Reaction equation

HRID 2039008 reaction equation
CN1CCOCC1.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:33])[CH2:16][NH:17][C:18]([CH2:20][N:21]([CH2:29][C:30](O)=[O:31])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:19])=[CH:11][CH:10]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:59][O:60][C:61](=[O:67])[C@@H:62]([CH:64]([CH3:66])[CH3:65])[NH2:63]>CN(C)C=O>[CH3:59][O:60][C:61](=[O:67])[CH:62]([NH:63][C:30](=[O:31])[CH2:29][N:21]([CH2:20][C:18](=[O:19])[NH:17][CH2:16][C:15]([C:12]1[CH:13]=[CH:14][C:9]([Br:8])=[CH:10][CH:11]=1)=[O:33])[C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH:64]([CH3:66])[CH3:65]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11984198Methyl D-valinate hydrochlorideHCID 59611182({[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetic acid

Product 1

HCID 666202862-[2-({[2-(4-Bromo-phenyl)-2-oxo-ethyl carbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetylamino]-3-methyl-butyric acid methyl esterYield 87.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Methylmorpholine (4.1 mL, 37.3 mmol) was added to a suspension of ({[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetic acid (4 g, 9.3 mmol), and HATU (4.61 g, 12.1 mmol) in dimethylformamide (25 mL). After 5 minutes d-valine methyl ester hydrochloride (1.56 g, 9.3 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 (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to yield 2-[2-({[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-methyl}-tert-butoxycarbonyl-amino)-acetylamino]-3-methyl-butyric acid methyl ester (4.37 g, 8.1 mmol, 87%). C23H32BrN3O7 calculated 541.1 observed [M+1]+ 431.1; rt=2.65 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-b9a3ad838d144138a3cefd1e6d91ceca
Source dataset
uspto-grants-2013_11
Patent number
US08575118B2

Reaction notes

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