1-(Chloromethyl)-4-methanesulfonylbenzene → 2,4-Difluoro-5(p-methylsulfonylbenzyl)-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid

HRID 867453Notes

Reaction equation

HRID 867453 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[NH:7][C:6]1[CH2:12][CH:13]([CH2:17][C:18]([OH:20])=[O:19])[CH2:14][CH2:15][CH2:16][C:5]2=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:31][S:32]([C:35]1[CH:42]=[CH:41][C:38]([CH2:39]Cl)=[CH:37][CH:36]=1)(=[O:34])=[O:33]>O1CCCC1.C1(C)C=CC=CC=1.O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH2:39][C:38]1[CH:37]=[CH:36][C:35]([S:32]([CH3:31])(=[O:34])=[O:33])=[CH:42][CH:41]=1)[C:6]1[CH2:12][CH:13]([CH2:17][C:18]([OH:20])=[O:19])[CH2:14][CH2:15][CH2:16][C:5]2=1

Participants

7

Reactant 3

HCID 1235301-(Chloromethyl)-4-methanesulfonylbenzeneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 143712452,4-Difluoro-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid

Product 1

HCID 143712462,4-Difluoro-5(p-methylsulfonylbenzyl)-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold solution (0° C.) of 3.5 g of acid from Step 2 in 75 mL of tetrahydrofuran was added dropwise 38.7 cc of a solution of KHMDS in toluene (0.684M) and the mixture stirred for 10 minutes. To the resulting cold (0° C.) solution was added dropwise 3.5 g of a solution of p-methylsufonylbenzyl chloride in 10 mL of tetrahydrofuran. The reaction mixture was then stirred at room temperature for 6 hours. The reaction mixture was diluted with water and washed with Et2O. The aqueous layer was acidified with HCl (1N) and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated to dryness. The residue was triturated with a mixture of hexane/ethyl acetate (7:3) and filtered to yield the title product m.p. 200°-202° C.

Workup

  1. stirringThe reaction mixture was then stirred at room temperature for 6 hours
  2. washwashed with Et2O
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated to dryness
  7. customThe residue was triturated with a mixture of hexane/ethyl acetate (7:3)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-741dd9fda37a4680af4fbfa499c83729
Source dataset
uspto-grants-1988_10
Patent number
US04775680

Reaction notes

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