Chloromethyl methyl sulfide → 3-[[5-Chloro-2-(methylthiomethoxy)phenyl]methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one

HRID 1636446Notes

Reaction equation

HRID 1636446 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:25])=[C:6]([CH2:8][N:9]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[O:11][C:10]2=[O:24])[CH:7]=1.[H-].[Na+].[CH3:28][S:29][CH2:30]Cl>CN(P(N(C)C)(N(C)C)=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH2:28][S:29][CH3:30])=[C:6]([CH2:8][N:9]2[N:13]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:18][CH:19]=3)[O:11][C:10]2=[O:24])[CH:7]=1

Participants

5

Reactant 3

HCID 16916Chloromethyl methyl sulfideHCID 24758Sodium hydrideHCID 10474339Bms-191011

Product 1

HCID 193514983-[[5-Chloro-2-(methylthiomethoxy)phenyl]methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-oneYield 70%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent2×

Procedure

A solution of 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one (6.0 g, 16.2 mmol) in dry HMPA (50 mL) was added dropwise under nitrogen to a stirred suspension of sodium hydride (0.77 g of 60% dispersion in mineral oil, 19.4 mmol) in HMPA (15 mL). The resultant yellow solution was stirred for 30 min and then neat chloromethyl methyl sulfide (1.49 mL, 17.8 mmol) was added dropwise. The reaction mixture was stirred at room temperature overnight and the product was extracted with ethyl acetate (500 mL). The EtOAc layer was washed with satd. NaHCO3, water, brine and then dried (MgSO4). Rotary evaporation of EtOAc gave a yellow semi-solid which was recrystallized from ethyl acetate/hexanes to afford the title compound as white crystals (4.4 g, 70%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. extractionthe product was extracted with ethyl acetate (500 mL)
  3. washThe EtOAc layer was washed with satd
  4. dry with materialNaHCO3, water, brine and then dried (MgSO4)
  5. customRotary evaporation of EtOAc
  6. customgave a yellow semi-solid which
  7. customwas recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-cd2e3ee19c294406ba43b38b6369819a
Source dataset
uspto-grants-2000_03
Patent number
US06034113

Reaction notes

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