Benzylethanolamine → (R)-tert-butyl (1-(benzyl(2-hydroxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate

HRID 1521476Notes

Reaction equation

HRID 1521476 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]([NH:23][CH2:24][CH2:25][OH:26])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl.O>[CH2:16]([N:23]([CH2:24][CH2:25][OH:26])[C:10](=[O:12])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH:13]([CH3:15])[CH3:14])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 4348BenzylethanolamineHCID 8471TriethylamineHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 58602496(R)-tert-butyl (1-(benzyl(2-hydroxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamateYield 90.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-((tert-butoxycarbonyl)amino)-3-methylbutanoic acid (2.0 g, 9.20 mmol) in CH2Cl2 (40 mL) were added 2-(benzylamino)ethanol (1.3 g, 8.80 mmol), HATU (5.30 g, 13.8 mmol) and Et3N (2.80 g, 27.6 mmol) under N2. The mixture was stirred at rt overnight. The mixture was diluted with water (20 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography on silica gel to afford (R)-tert-butyl (1-(benzyl(2-hydroxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate (2.80 g, 88% yield) as a white solid. LC-MS m/z 351.2 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×30 mL)
  2. washThe combined organic layers were washed with brine (20 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by column chromatography on silica gel

Sources & evidence

ORD record
ord-e4fac316f6ba413386187f6f35f01f20
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

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