1-Methylimidazole → HCID 131723158, compound

HRID 840160Notes

Reaction equation

HRID 840160 reaction equation
C([Li])CCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.[Cl:12][Si](CC)(CC)CC.ClC1C=CC([C:27]([C:29]2[CH:30]=[CH:31][C:32]3[C:33]([CH:44]=2)=[C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[C:39](Cl)[CH:38]=2)[O:35][N:36]=3)=[O:28])=CC=1>C1COCC1>[Cl:12][C:40]1[CH:41]=[CH:42][C:37]([C:34]2[O:35][N:36]=[C:32]3[CH:31]=[CH:30][C:29]([CH:27]([C:11]4[N:7]([CH3:6])[CH:8]=[N:9][CH:10]=4)[OH:28])=[CH:44][C:33]=23)=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 22136476(4-Chlorophenyl)[3-(3-chlorophenyl)-2,1-benzisoxazol-5-yl]methanoneHCID 178418339Butyllithium2×

Product 1

HCID 131723158HCID 131723158, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

Butyllithium in hexanes (10 ml) was added slowly at −70° C. under N2 flow to a solution of 1-methylimidazole (1.31 g) in THF (30 ml). The mixture was stirred at −70° C. for 45 minutes. Chlorotriethylsilane (2.7 ml) was added. The mixture was allowed to warm to 15° C. and cooled to −70° C. Butyllithium (10 ml) was added slowly. The mixture was stirred at −70° C. for 1 hour, allowed to warm to −15° C. and cooled to −70° C. A solution of intermediate (6-b) (4.9 g) in THF (60 ml) was added. The mixture was stirred at −70° C. for 30 minutes, then hydrolyzed with water, extracted with ethyl acetate and decanted. The organic layer was dried, filtered and the solvent was evaporated. The residue (8.2 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.2) and crystallized from 2-propanone/diethyl ether. The precipitate was filtered off and dried, yielding 1.5 g (25%) of (±)-3-(3-chlorophenyl)-α-(4-chlorophenyl-α-(1-methyl-1H-imidazol-5-yl)-2,1-benzisoxazole-5-methanol (interm. 6-c).

Workup

  1. temperatureto warm to 15° C.
  2. temperaturecooled to −70° C
  3. stirringThe mixture was stirred at −70° C. for 1 hour
  4. temperatureto warm to −15° C.
  5. temperaturecooled to −70° C
  6. stirringThe mixture was stirred at −70° C. for 30 minutes
  7. extractionhydrolyzed with water, extracted with ethyl acetate
  8. customdecanted
  9. customThe organic layer was dried
  10. filtrationfiltered
  11. customthe solvent was evaporated
  12. customThe residue (8.2 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.2)
  13. customcrystallized from 2-propanone/diethyl ether
  14. filtrationThe precipitate was filtered off
  15. customdried

Sources & evidence

ORD record
ord-fc03a4aecee5468c81ab32b45f1af0a6
Source dataset
uspto-grants-2002_04
Patent number
US06365600B1

Reaction notes

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