2,4-Dichlorobenzyl chloride → HCID 57810470, compound

HRID 1818008Notes

Reaction equation

HRID 1818008 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([F:14])[CH:7]=[C:8]2[C:12]=1[NH:11][CH:10]=[C:9]2[CH3:13].[Cl:15][C:16]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:17]=1[CH2:18]Cl.Cl.O.CCOCC>CN(C=O)C.CCOCC>[Br:3][C:4]1[CH:5]=[C:6]([F:14])[CH:7]=[C:8]2[C:12]=1[N:11]([CH2:18][C:17]1[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:16]=1[Cl:15])[CH:10]=[C:9]2[CH3:13]

Participants

7

Reactant 4

HCID 72122,4-Dichlorobenzyl chlorideHCID 24758Sodium hydrideHCID 534012037-Bromo-5-fluoro-3-methyl-1H-indoleHCID 86604269HCID 86604269, compound

Product 1

HCID 57810470HCID 57810470, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

NaH (60% in oil, 526 mg, 13.15 mmol, 1.5 equiv.) was added to a solution of 7-bromo-5-fluoro-3-methyl-1H-indole, [which was prepared analogous to I-30, according to the method of Dobbs, A., J. Org. Chem., 66, 638-641 (2001)], (2 g, 8.77 mmol, 1 equiv.) in DMF (30 mL) at −10° C. Reaction mixture was warmed to rt and stirred for 30 min. A solution of 2,4-dichlorobenzyl chloride (2.06 g, 10.52 mmol, 1.2 equiv.) in DMF (10 mL) was added gradually over 2.5 min at −10° C. The reaction mixture was allowed to warm to rt and stirred for 1 h. The reaction mixture was poured into a stirred solution of 10% HCl/water/ether (1:1:2, 40 mL) mixture, and the aqueous layer was extracted with ether (2×10 mL). The combined organic layers were washed with water (3×75 mL), brine (75 mL), dried over MgSO4, filtered, and concentrated to afford crude product as brown solid. Ether (4 mL) was added to the crude product, cooled down to −78° C. and filtered to afford I-191 (2.49 g, 73%) as off-white solid. 1H-NMR (500 MHz, CDCl3) confirmed the structure.

Workup

  1. custom[which was prepared analogous to I-30
  2. customat −10° C
  3. customReaction mixture
  4. temperatureto warm to rt
  5. stirringstirred for 1 h
  6. extractionthe aqueous layer was extracted with ether (2×10 mL)
  7. washThe combined organic layers were washed with water (3×75 mL), brine (75 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford crude product as brown solid
  12. temperaturecooled down to −78° C.
  13. filtrationfiltered
  14. customto afford I-191 (2.49 g, 73%) as off-white solid

Sources & evidence

ORD record
ord-308c252fde4d407684d94daeff5c6831
Source dataset
uspto-grants-2009_10
Patent number
US07598397B2

Reaction notes

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