alpha-Bromo-o-chlorotoluene → 9-[(2-Chlorophenyl)methyl]-6,8-difluoro-2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid

HRID 1382838Notes

Reaction equation

HRID 1382838 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([F:15])[CH:14]=1)[NH:11][C:10]1[CH:9]([CH2:16][C:17]([OH:19])=[O:18])[CH2:8][CH2:7][CH2:6][C:5]2=1.[H-].[Na+].[Cl:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25]Br>CN(C=O)C.O>[Cl:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25][N:11]1[C:10]2[CH:9]([CH2:16][C:17]([OH:19])=[O:18])[CH2:8][CH2:7][CH2:6][C:5]=2[C:4]2[C:12]1=[C:13]([F:15])[CH:14]=[C:2]([F:1])[CH:3]=2

Participants

6

Reactant 3

HCID 11905alpha-Bromo-o-chlorotolueneHCID 24758Sodium hydrideHCID 14372496HCID 14372496, compound

Product 1

HCID 143725099-[(2-Chlorophenyl)methyl]-6,8-difluoro-2,3,4,9-tetrahydro-1H-carbazole-1-acetic acidYield 33.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 200 mg of 6,8-difluoro-1,2,3,4-tetrahydrocarbazol-1-yl-acetic acid from Example 34 step II in 8 cc of DMF was added portionwise 40 mg of sodium hydride. The resulting mixture was stirred for 30 minutes at room temperature and 185 mg of o-chloro-benzyl bromide was then added. After stirring overnight at room temperature, the resulting mixture was diluted with water and washed with ether. The aqueous layer was acidified with (1N) HCl and extracted with ether. The ethereal layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The crude product was purified on preparative plates (silica gel) eluting with CHCl3 :MeOH:NH4OH (8:4:1) to yield 98 mg of pure title product. m.p. 197°-198° C.

Workup

  1. stirringAfter stirring overnight at room temperature
  2. washwashed with ether
  3. extractionextracted with ether
  4. washThe ethereal layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. customThe crude product was purified on preparative plates (silica gel)
  8. washeluting with CHCl3 :MeOH:NH4OH (8:4:1)

Sources & evidence

ORD record
ord-0564b2d42bc64564aff1b757c5939312
Source dataset
uspto-grants-1989_02
Patent number
US04808608

Reaction notes

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