Hydrochloric Acid → HCID 58788378, compound

HRID 2374740Notes

Reaction equation

HRID 2374740 reaction equation
[C:1]([C:4]1[S:5][CH:6]=[CH:7][C:8]=1[N:9]([C:16](=O)[CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[C:20]=1[F:26])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])(=[O:3])[NH2:2].[H-].[Na+].Cl>CN(C=O)C.CCOCC>[F:26][C:20]1[C:21]([F:25])=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][CH2:17][C:16]1[N:9]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:8]2[CH:7]=[CH:6][S:5][C:4]=2[C:1](=[O:3])[N:2]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 58788225HCID 58788225, compound

Product 1

HCID 58788378HCID 58788378, compoundYield 78.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Procedure

Ethyl 2-((2-carbamoylthiophen-3-yl)-(3-(2,3-difluorophenyl)propanoyl)amino)acetate (Int. B56) (500 mg) in dry DMF (3 ml) was cooled in an ice bath and treated portion wise with sodium hydride (50 mg, 60% dispersion in oil). The reaction mixture was stirred at room temperature for 30 min to give an orange homogeneous solution. Excess 1 M hydrogen chloride in ether was added giving a pale yellow solution and a precipitate. The mixture was heated in an oil bath at 120° C. for 30 min. The solution was concentrated and re-dissolved in ethyl acetate. The solution was washed with saturated sodium bicarbonate, brine, dried and concentrated in vacuo to give a solid. Trituration with ether afforded the title compound as a white solid (375 mgs, 78%); 1H-NMR (CDCl3) δ 1.29 (3H, t), 3.01 (2H, t), 3.30 (2H, t), 4.29 (2H, q), 4.84 (2H, s), 6.96 (1H, d), 7.03, (3H, m) and 7.77 (1H, d). (APCI+) Found (M+1)=379, C18H16F2N2O3S requires 378.

Workup

  1. customto give an orange homogeneous solution
  2. customgiving a pale yellow solution
  3. temperatureThe mixture was heated in an oil bath at 120° C. for 30 min
  4. concentrationThe solution was concentrated
  5. dissolutionre-dissolved in ethyl acetate
  6. washThe solution was washed with saturated sodium bicarbonate, brine
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customto give a solid

Sources & evidence

ORD record
ord-f99da05afdc9497998551d84ed78f874
Source dataset
uspto-grants-2008_12
Patent number
US07462620B2

Reaction notes

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