Sodium Azide → (S)-Methyl 3-(4-(2-azidoethoxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanoate

HRID 1504358Notes

Reaction equation

HRID 1504358 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1.[N-:25]=[N+:26]=[N-:27].[Na+]>CN(C=O)C.O>[N:25]([CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1)=[N+:26]=[N-:27]

Participants

5

Reactant 2

HCID 33557Sodium AzideHCID 86684665HCID 86684665, compound

Product 1

HCID 86684664(S)-Methyl 3-(4-(2-azidoethoxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanoateYield 100.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1A (1.61 g, 4.0 mmol) and sodium azide (0.78 g, 12.0 mmol) in DMF (27 mL) was stirred at room temperature for 20 h. The reaction mixture was diluted with H2O (120 mL) and extracted with EtOAc (3×60 mL). The combined organic phases were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, step-wise gradient from 2-40% EtOAc in Hexanes) to give 2A (1.46 g, 100%) as a clear oil. 1H NMR (600 MHz, CDCl3): δ 7.05 (2H, d, J=8.4 Hz), 6.85 (2H, d, J=8.4 Hz), 4.97 (1H, d, J=7.8 Hz), 4.51-4.58 (1H, m), 4.13 (2H, t, J=5.4 Hz), 3.71 (3H, s), 3.58 (2H, t, J=5.4 Hz), 3.06 (1H, dd, J=13.8, 5.4 Hz), 3.00 (1H, dd, J=13.8, 5.4 Hz), 1.42 (9H, s); 13C NMR (150 MHz, CDCl3): δ 172.3, 157.3, 155.1, 130.4, 128.7, 114.6, 79.9, 66.9, 54.5, 52.2, 50.2, 37.5, 28.3; MS (ESI, m/z): 387 (M+Na)+.

Workup

  1. extractionextracted with EtOAc (3×60 mL)
  2. washThe combined organic phases were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography (SiO2, step-wise gradient from 2-40% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-1a5ee99c4e644eb2a6bd4dc92e2ee050
Source dataset
uspto-grants-2015_12
Patent number
US09212381B2

Reaction notes

Loading…