Hydrochloric Acid → 5-tert-Butyl-2-(2-nitro-phenylamino)-thiophene-3-carbonitrile

HRID 131374Notes

Reaction equation

HRID 131374 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:9]([CH3:12])([CH3:11])[CH3:10])=[CH:5][C:6]=1[C:7]#[N:8].[H-].[Na+].F[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[N+:22]([O-:24])=[O:23].Cl>C1COCC1>[C:9]([C:4]1[S:3][C:2]([NH:1][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N+:22]([O-:24])=[O:23])=[C:6]([C:7]#[N:8])[CH:5]=1)([CH3:12])([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 738951-Fluoro-2-nitrobenzeneHCID 210934642-Amino-5-tert-butylthiophene-3-carbonitrile

Product 1

HCID 210935385-tert-Butyl-2-(2-nitro-phenylamino)-thiophene-3-carbonitrileYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Add a solution of 2-amino-5-tert-butyl-thiophene-3-carbonitrile (16.9 g, 94 mmol) in THF (50 mL) to a mixture of washed NaH (from 6.76 g of 60% mineral oil dispersion) in THF (200 mL) in a water bath at room temperature. Stir 15 minutes, then add a solution of 2-fluoro-nitrobenzene (13.2 g, 94 mmol) in THF (50 mL) dropwise. Stir overnight. Pour the purple reaction mixture unto 6 N HCl (400 mL). Extract the mixture with diethyl ether (400 mL). Wash the ether layer with 2 N HCl (400 mL), brine (250 mL), dry (Na2SO4), and concentrate to afford a mixture of crystals in a dark oily residue. Triturate the crystals with hexanes and filter to afford the title compound as a red powder (21.2 g, 75%) mp 85-90° C.: 1H NMR (CDCl3) δ 1.39 (s, 9H), 6.81 (s, 1H), 6.97 (t, 1H), 7.23 (d, 1H), 7.53 (t, 1H), 8.25 (d, 1H), 9.66 (bs, 1H).

Workup

  1. stirringStir overnight
  2. extractionExtract the mixture with diethyl ether (400 mL)
  3. washWash the ether layer with 2 N HCl (400 mL), brine (250 mL)
  4. dry with materialdry (Na2SO4)
  5. concentrationconcentrate
  6. customto afford
  7. additiona mixture of crystals in a dark oily residue
  8. customTriturate the crystals with hexanes
  9. filtrationfilter

Sources & evidence

ORD record
ord-2022018e50f241c88773731bc7bd738c
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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