Ethyl Bromide → HCID 90411361, compound

HRID 627067Notes

Reaction equation

HRID 627067 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:15][CH2:14][C:13]2[C:12]3[NH:16][CH:17]=[CH:18][C:11]=3[S:10][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].[H-].[Na+].[CH2:21](Br)[CH3:22]>CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[CH2:15][CH2:14][C:13]2[C:12]3[N:16]([CH2:21][CH3:22])[CH:17]=[CH:18][C:11]=3[S:10][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 24758Sodium hydrideHCID 90410906HCID 90410906, compound

Product 1

HCID 90411361HCID 90411361, compoundYield 78.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of the product of Example 1, step (g) (0.068 g, 0.26 mmol) in DMF (4 ml) at 0° C. under argon was added NaH (60% dispersion by wt., 0.015 g, 0.39 mmol) followed by ethyl bromide (0.029 ml, 0.39 mmol). The reaction mixture was stirred at 0° C. for 2 hrs and then quenched by slow addition of saturated aqueous citric acid (40 ml). The aqueous mixture was extracted with DCM (3×). The combined DCM extracts were washed with water (2×), brine, dried (MgSO4), filtered, and solvent evaporated in vacuo to give the crude product. Purification by silica-gel chromatography (gradient elution: 0 to 50% EtOAc in hexanes) gave the sub-titled compound as a tan solid (0.060 g). 1H NMR (CDCl3) δ 6.75 (d, J=3.0 Hz, 1 H), 6.24 (d, J=3.0 Hz, 1H), 4.40-4.08 (m, 4H), 3.96-3.62 (m, 4 H), 3.34-2.92 (m, 4 H), 1.42 (t, J=6.9 Hz, 3 H), 1.28 (t, J=6.9 Hz, 3H); MS: ESI (positive): 293 (M+H).

Workup

  1. customquenched by slow addition of saturated aqueous citric acid (40 ml)
  2. extractionThe aqueous mixture was extracted with DCM (3×)
  3. washThe combined DCM extracts were washed with water (2×), brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customsolvent evaporated in vacuo
  7. customto give the crude product
  8. customPurification
  9. washby silica-gel chromatography (gradient elution: 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-35bc40bc4d6d410aa3619f85adf080df
Source dataset
uspto-grants-2016_04
Patent number
US09309262B2

Reaction notes

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