Sodium Azide → 5-((2S)-3-Azido-2-hydroxy-propoxy)-2-methyl-1H-indole-3-carboxylic acid ethyl ester

HRID 1794792Notes

Reaction equation

HRID 1794792 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:16][CH:17]3[CH2:19][O:18]3)[CH:13]=2)[NH:8][C:7]=1[CH3:20])=[O:5])[CH3:2].[N-:21]=[N+:22]=[N-:23].[Na+].[Cl-].[Li+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:16][C@@H:17]([OH:18])[CH2:19][N:21]=[N+:22]=[N-:23])[CH:13]=2)[NH:8][C:7]=1[CH3:20])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 33557Sodium AzideHCID 433294Lithium ChlorideHCID 86584563HCID 86584563, compound

Product 1

HCID 865845645-((2S)-3-Azido-2-hydroxy-propoxy)-2-methyl-1H-indole-3-carboxylic acid ethyl esterYield 38.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1.4 g (5.1 mmol) of 2-methyl-5-oxiranylmethoxy-1H-indole-3-carboxylic acid ethyl ester (which was obtained in Example 139), 0.5 g (7.6 mmol) of sodium azide and 0.43 g (10.2 mmol) of lithium chloride in 15 mL anhydrous DMF was heated at 60° C. overnight. The mixture was cooled to room temperature and quenched with water. The aqueous mixture was extracted with ethyl acetate. The organic layer was washed twice with water, dried over sodium sulfate and concentrated in vacuo. The residue was then purified by flash chromatography (10% EtOAc in hexanes to 50% EtOAc in hexanes) to give 0.63 g of the title compound as a yellow solid; mp 75–77° C.; 1H NMR (300 MHz, DMSO-d6) δ 1.34 (t, J=7.1 Hz, 3H), 2.66 (s, 3H), 3.42 (d, 4.6 Hz, 1H), 3.89–3.95 (m, 2H), 4.00–4.06 (m, 1H), 4.26 (q, J=7.1 Hz, 2H), 5.55 (d, J=5.1 Hz, 2H), 6.76 (dd, J=8.7, 2.7 Hz, 1H), 7.24 (d, J=8.7 Hz, 1H), 7.43 (d, J=2.4 Hz, 1H), 11.65 (s, 1H); MS (ES) m/z: 319.0 (MH+); HRMS Calcd. for C15H18N4O4(M+): 318.1328. Found: 318.1334.

Workup

  1. customquenched with water
  2. extractionThe aqueous mixture was extracted with ethyl acetate
  3. washThe organic layer was washed twice with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was then purified by flash chromatography (10% EtOAc in hexanes to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e4cf6f6e5dd345f8b3d595cbc6f9274a
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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