Ethyl isothiocyanate → 2,3-Diazaspiro[4.4]non-3-ene-2-carbothioic acid ethylamide

HRID 1484429Notes

Reaction equation

HRID 1484429 reaction equation
Cl.[CH:2]1[C:6]2([CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:5][NH:4][N:3]=1.[CH2:11]([N:13]=[C:14]=[S:15])[CH3:12].C(N(C(C)C)CC)(C)C>CO.O>[CH2:11]([NH:13][C:14]([N:3]1[N:4]=[CH:5][C:6]2([CH2:10][CH2:9][CH2:8][CH2:7]2)[CH2:2]1)=[S:15])[CH3:12]

Participants

6

Reactant 3

HCID 10966Ethyl isothiocyanateHCID 81531DiisopropylethylamineHCID 673605592,3-Diaza-spiro[4.4]non-1-ene hydrochloride

Product 1

HCID 533541352,3-Diazaspiro[4.4]non-3-ene-2-carbothioic acid ethylamideYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

2,3-Diaza-spiro[4.4]non-1-ene hydrochloride (15.4 g, 95.9 mmol; isolated from reaction of 2,3-diaza-spiro[4.4]non-2-ene, synthesized as described in WO 2008/034863, with HCl in isopropanol/toluene) was taken up in a mixture of 70 mL methanol and 30 mL water. Ethyl isothiocyanate (10.09 g, 115.1 mmol) was added using an addition funnel, and the funnel was rinsed with 40 mL methanol. At 30° C., diisopropylethylamine (14.8 g, 114.5 mmol) was added dropwise over a period of 10 minutes, and the addition funnel was rinsed with 7 mL water. After stirring the reaction mixture for 1 hour at 30° C., the mixture was cooled to 10° C. over a period of 1 hour and subsequently stirred at this temperature for another 2 hours. The precipitate was isolated by filtration, washed twice with 20 mL of a cold 3:1 mixture of methanol and water and dried at 50° C. under reduced pressure to give 16.8 g (83%) of 2,3-diaza-spiro[4.4]non-3-ene-2-carbothioic acid ethylamide as a white to off-white solid. 1H NMR identical to spectrum obtained from material prepared on small scale (vide supra).

Workup

  1. washthe funnel was rinsed with 40 mL methanol
  2. washthe addition funnel was rinsed with 7 mL water
  3. temperaturethe mixture was cooled to 10° C. over a period of 1 hour
  4. stirringsubsequently stirred at this temperature for another 2 hours
  5. customThe precipitate was isolated by filtration
  6. washwashed twice with 20 mL of a cold 3:1 mixture of methanol and water
  7. customdried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-c698973c7f1048b995bf3a6b1fc63cd3
Source dataset
uspto-grants-2016_08
Patent number
US09422244B2

Reaction notes

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