Acetic Acid → HCID 10360849, compound

HRID 2221119Notes

Reaction equation

HRID 2221119 reaction equation
[S:1]1[C:5]([CH:6]=O)=[CH:4][C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]1=2.[CH2:12]([O:15][C:16](=[O:28])[NH:17][C:18]1[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=1[N+:25]([O-])=O)[CH2:13][CH3:14].[BH3-]C#N.[Na+].CC(O)=O.O.[Cl-].[Na+].O.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(#N)C.O>[CH2:12]([O:15][C:16](=[O:28])[NH:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][CH2:6][C:5]2[S:1][C:2]3[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=3[CH:4]=2)=[CH:20][C:19]=1[NH2:25])[CH2:13][CH3:14]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 24489Sodium DithioniteHCID 7365001-Benzothiophene-2-carbaldehydeHCID 5003444Sodium cyanoborohydrideHCID 23713072Sodium chloride dihydrateHCID 69274011HCID 69274011, compound

Product 1

HCID 10360849HCID 10360849, compoundYield 10.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

Benzo[b]thiophene-2-carbaldehyde (1.36 g, 8.38 mmol) was added to a solution of (4-amino-2-nitro-phenyl)-carbamic acid propyl ester (2.00 g, 8.36 mmol) in acetonitrile (10 mL). The mixture was heated to 160° C. for 2 minutes in a 20 mL sealed microwave process vial. Upon cooling NaBH3CN (1.06 g, 16.7 mmol) and AcOH (48 μL, 0.84 mmol) were added and the mixture was stirred for 30 minutes at 25° C. Water/brine (1:1, 100 mL) was added and the mixture was extracted with ethyl acetate (3×100 mL). The organic phase was dried over magnesium sulphate, filtered and concentrated in vacuo. The crude intermediate was purified by flash chromatography on silica gel (eluent: ethyl acetate:heptane 1:9), and evaporated to dryness. The intermediate was then dissolved in tetrahydrofuran (20 mL) and Na2S2O4 (3.67 g, 21 mmol) dissolved in water (50 mL) was added. The resulting mixture was stirred at 40° C. for 5 hours under argon. The resulting mixture was extracted with ethyl acetate (3×100 mL), the combined organic phases dried over magnesium sulphate, filtered, and concentrated in vacuo. Purification by flash chromatography (eluent: ethyl acetate:heptane 1:1) furnished 0.3 g (10%) of the title compound as a solid. LC/MS (m/z) 356 ([M+H]+); RT=2.45 min. 1H NMR (CDCl3): 0.95 (t, 3H); 1.67 (m, 2H); 4.08 (t, 2H); 4.55 (s, 2H); 6.08 (d, 1H); 6.13 (dd, 1H); 6.93 (d, 1H); 7.20 (s, 1H); 7.27 (dt, 1H); 7.32 (dt, 1H); 7.68 (d, 1H); 7.77 (d, 1H).

Workup

  1. customsealed microwave process vial
  2. additionwere added
  3. extractionthe mixture was extracted with ethyl acetate (3×100 mL)
  4. dry with materialThe organic phase was dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude intermediate was purified by flash chromatography on silica gel (eluent: ethyl acetate:heptane 1:9)
  8. customevaporated to dryness
  9. dissolutionThe intermediate was then dissolved in tetrahydrofuran (20 mL)
  10. additionwas added
  11. stirringThe resulting mixture was stirred at 40° C. for 5 hours under argon
  12. extractionThe resulting mixture was extracted with ethyl acetate (3×100 mL)
  13. dry with materialthe combined organic phases dried over magnesium sulphate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customPurification by flash chromatography (eluent: ethyl acetate:heptane 1:1)

Sources & evidence

ORD record
ord-5dccd46f610f4c4888316517db716343
Source dataset
uspto-grants-2008_05
Patent number
US07368472B2

Reaction notes

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