Tetrahydrofuran → HCID 21074313, compound

HRID 2053708Notes

Reaction equation

HRID 2053708 reaction equation
[CH3:1][N:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)[C:3](=O)[CH3:4].C1COCC1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:20].CCCCCCC>C(Cl)Cl>[CH3:1][N:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)[C:3](=[S:20])[CH3:4]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8900HeptaneHCID 14817Phosphorus sulfide (P2S5)HCID 21947447N-[(4-Fluorophenyl)methyl]-N-methylacetamide

Product 1

HCID 21074313HCID 21074313, compoundYield 91.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Combine N-methyl-N-(4-fluorobenzyl)acetamide (364.8 g, 2.01 mol) and THF (9 L). Stir to dissolve and then add phosphorus pentasulfide (537.7 g, 1.21 mol). After 45 min heat to reflux for 3 h, then cool and stir overnight to give a solid. Collect the solid by filtration and rinse the cake with THF (4 L), evaporate the filtrate in vacuo to give a residue, dissolve the residue in methylene chloride (about 500 mL), and passed over a cake of silica gel 60 (1.2 kg) preconditioned with heptane. Elute with 4 L of heptane/methylene chloride (1:1) followed by 100% methylene chloride to afford 217.98 g of N-methyl-N-(4-fluorobenzyl)thioacetamide (55%): mp=99-104° C.; Rf=0.42 (methylene chloride); 1H NMR (CDCl3) 7.35-7.26 (m, 1), 7.14-6.96 (m, 3),5.28 (s, 1.2) and 4.79 (s, 0.8), 3.42 (s, 1.2) and 3.15 (s, 1.8), 2.72 (s, 1.2) and 2.69 (s, 1.8). Note: Partial protons are believed to be due to rotomers.

Workup

  1. dissolutionto dissolve
  2. temperatureAfter 45 min heat
  3. temperatureto reflux for 3 h
  4. temperaturecool
  5. stirringstir overnight
  6. customto give a solid
  7. customCollect the solid
  8. filtrationby filtration
  9. washrinse the cake with THF (4 L)
  10. customevaporate the filtrate in vacuo
  11. customto give a residue
  12. washElute with 4 L of heptane/methylene chloride (1:1)

Sources & evidence

ORD record
ord-938adbf72f7c4c398b31bf97c40a42ee
Source dataset
uspto-grants-2008_02
Patent number
US07326731B2

Reaction notes

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