4-Methylmorpholine → Benzyl 1-(2,2-dimethoxyethylamino)-2-methyl-1-oxopropan-2-ylcarbamate

HRID 927346Notes

Reaction equation

HRID 927346 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:17])([CH3:16])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:49][O:50][CH:51]([O:54][CH3:55])[CH2:52][NH2:53]>CN(C=O)C>[CH3:49][O:50][CH:51]([O:54][CH3:55])[CH2:52][NH:53][C:13](=[O:15])[C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 89728Aminoacetaldehyde dimethyl acetalHCID 294936N-((Benzyloxy)carbonyl)-2-methylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 86674736Benzyl 1-(2,2-dimethoxyethylamino)-2-methyl-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(benzyloxycarbonylamino)-2-methylpropanoic acid (20 g, 0.084 mol), HATU (CAN 148893-10-1, 41.56 g, 0.11 mol) and N-methylmorpholine (CAN 109-02-4, 25.54 g, 0.253 mol) in DMF (400 mL) was stirred at room temperature for 10 min. 2,2-Dimethoxyethanamine (CAN 22483-09-6, 9.75 g, 0.093 mol) was added and the mixture was stirred overnight. After evaporation of solvents, the residue was diluted with methylene chloride (500 mL) and saturated sodium bicarbonate solution (500 mL). After being separated, the organic layer was washed with 5 N citric acid solution (500 mL), brine (500 mL) and dried over anhydrous sodium sulfate. Removal of the solvent under reduced pressure left a yellow oil (27 g, 99%) which was used in the next reaction step without further purification. 1H NMR (300 MHz, CDCl3): δ 7.36-7.33 (m, 5H), 6.44-6.38 (b, 1H), 5.31 (s, 1H), 5.09 (s, 2H), 4.34-4.33 (m, 1H), 3.40-3.37 (m, 8H), 2.06-2.03 (m, 6H).

Workup

  1. stirringthe mixture was stirred overnight
  2. customAfter evaporation of solvents
  3. additionthe residue was diluted with methylene chloride (500 mL) and saturated sodium bicarbonate solution (500 mL)
  4. customAfter being separated
  5. washthe organic layer was washed with 5 N citric acid solution (500 mL), brine (500 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customRemoval of the solvent under reduced pressure
  8. waitleft a yellow oil (27 g, 99%) which
  9. customwas used in the next reaction step without further purification

Sources & evidence

ORD record
ord-984d6af654cb4203acaa714e658365f7
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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