Ammonium Chloride → 3-(3-Chlorophenyl)-alpha-(4-phenyl-2-thiazolyl)-2,1-benzisoxazole-5-methanol

HRID 1830802Notes

Reaction equation

HRID 1830802 reaction equation
[Li]CCCC.[C:6]1([C:12]2[N:13]=[CH:14][S:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[Cl:17][C:18]1[CH:19]=[C:20]([C:24]2[O:25][N:26]=[C:27]3[CH:32]=[CH:31][C:30]([CH:33]=[O:34])=[CH:29][C:28]=23)[CH:21]=[CH:22][CH:23]=1.[NH4+].[Cl-]>C1COCC1>[Cl:17][C:18]1[CH:19]=[C:20]([C:24]2[O:25][N:26]=[C:27]3[CH:32]=[CH:31][C:30]([CH:33]([C:14]4[S:15][CH:16]=[C:12]([C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=5)[N:13]=4)[OH:34])=[CH:29][C:28]=23)[CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 74581Thiazole, 4-phenyl-HCID 22048466HCID 22048466, compoundHCID 178418339Butyllithium

Product 1

HCID 220484773-(3-Chlorophenyl)-alpha-(4-phenyl-2-thiazolyl)-2,1-benzisoxazole-5-methanolYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

BuLi (0.118 mol) was added dropwise at −70° C. under N2 flow to a solution of 4-phenyl-thiazole (0.097 mol) in THF (205 ml). The mixture was stirred at −70° C. for 1 hour. A solution of intermediate (13) (0.0692 mol) in THF (205 ml) was added dropwise. The mixture was stirred at −70° C. for 2 hours, brought to -30° C. over a 90-min period, poured out into NH4Cl 10% and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue (39.5 g) was purified by column chromatography over silica gel (eluent: cyclohexane/EtOAc 80/20; 20–45 μm). The pure fractions were collected and the solvent was evaporated. A part (1.5 g) of the residue (18 g, 62%) was crystallized from 2-propanone. The precipitate was filtered off and dried, yielding 1.5 g (84%) of 3-(3-chlorophenyl)-α-(4-phenyl-2-thiazolyl)-2,1-benzisoxazole-5-methanol (intermediate 14), mp. 136° C.

Workup

  1. stirringThe mixture was stirred at −70° C. for 2 hours
  2. waitbrought to -30° C. over a 90-min period
  3. extractionextracted with DCM
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue (39.5 g) was purified by column chromatography over silica gel (eluent: cyclohexane/EtOAc 80/20; 20–45 μm)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated
  11. customA part (1.5 g) of the residue (18 g, 62%) was crystallized from 2-propanone
  12. filtrationThe precipitate was filtered off
  13. customdried

Sources & evidence

ORD record
ord-3f9f7fd75eae41d986571984138a746c
Source dataset
uspto-grants-2006_06
Patent number
US07067531B2

Reaction notes

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