Triethylamine → (Z)-N-[5-Fluoro-2-methyl-1-(4-methylthiobenzylidene)inden-3-ylmethyl]-N'-hydroxy-N'-methyl urea

HRID 379629Notes

Reaction equation

HRID 379629 reaction equation
Cl.[CH3:2][NH:3][OH:4].C(N(CC)CC)C.[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)/[C:18](=[CH:22]\[C:23]1[CH:28]=[CH:27][C:26]([S:29][CH3:30])=[CH:25][CH:24]=1)/[C:17]([CH3:31])=[C:16]2[CH2:32][N:33]=[C:34]=[O:35]>C1COCC1>[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)/[C:18](=[CH:22]\[C:23]1[CH:28]=[CH:27][C:26]([S:29][CH3:30])=[CH:25][CH:24]=1)/[C:17]([CH3:31])=[C:16]2[CH2:32][NH:33][C:34]([N:3]([OH:4])[CH3:2])=[O:35]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77906N-methylhydroxylamine hydrochlorideHCID 86745524(Z)-5-Fluoro-2-methyl-1-(4-methylthiobenzylidene)inden-3-ylmethyl isocyanate

Product 1

HCID 10134627(Z)-N-[5-Fluoro-2-methyl-1-(4-methylthiobenzylidene)inden-3-ylmethyl]-N'-hydroxy-N'-methyl urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of N-methyl hydroxylamine hydrochloride (9.82 g, 117.6 mmol) in THF (150 mL) at room temperature there was added triethylamine (16.3 mL, 117.6 mmol) and the mixture stirred for 10 minutes. There was added, over 15 minutes, a solution of the isocyanate from Step 1 in THF (100 mL). After 2 hours of stirring at room temperature, the THF was evaporated and the residue, on trituration with water, afforded a yellow solid which was filtered. This solid was stirred in ether (150 mL) and filtered again. This crude material was chromatographed on silica gel eluting with 5% ethanol in methylene chloride. The more polar component of the mixture was stirred with methylene chloride (50 mL) for 2 hours and filtered and the solid crystallized from ethyl acetate to afford the pure title product as yellow crystals, mp 190-192° C. dec.

Workup

  1. additionThere was added, over 15 minutes
  2. stirringAfter 2 hours of stirring at room temperature
  3. customthe THF was evaporated
  4. customthe residue, on trituration with water, afforded a yellow solid which
  5. filtrationwas filtered
  6. stirringThis solid was stirred in ether (150 mL)
  7. filtrationfiltered again
  8. customThis crude material was chromatographed on silica gel eluting with 5% ethanol in methylene chloride
  9. stirringThe more polar component of the mixture was stirred with methylene chloride (50 mL) for 2 hours
  10. filtrationfiltered
  11. customthe solid crystallized from ethyl acetate

Sources & evidence

ORD record
ord-bafbf715b56b4c879245a33f5bc4a8b8
Source dataset
uspto-grants-2001_10
Patent number
US06300346B1

Reaction notes

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