2,4-Dichlorobenzyl chloride → HCID 57810473, compound

HRID 2106066Notes

Reaction equation

HRID 2106066 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]=[CH:12][C:13]([OH:15])=[O:14])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:16].CC(C)([O-])C.[K+].[Cl:23][C:24]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:25]=1[CH2:26]Cl>C1COCC1>[Cl:23][C:24]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:25]=1[CH2:26][N:7]1[C:8]2[C:4](=[CH:3][C:2]([F:1])=[CH:10][C:9]=2/[CH:11]=[CH:12]/[C:13]([OH:15])=[O:14])[C:5]([CH3:16])=[CH:6]1

Participants

5

Reactant 3

HCID 72122,4-Dichlorobenzyl chlorideHCID 23665647Potassium tert-butoxideHCID 534008313-(5-Fluoro-3-methyl-1H-indol-7-yl)prop-2-enoic acid

Product 1

HCID 57810473HCID 57810473, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(5-fluoro-3-methylindol-7-yl)acrylic acid, prepared as in Example 3 (20 g, 92 mmol) in 200 mL THF was added potassium t-butoxide (24.4 g, 206 mmol) in portions over approximately 10 min, while keeping the internal temperature below 18° C. with an ice-water bath. 2,4-Dichlorobenzyl chloride (21.7 g, 110 mmol) was added over a period of 5 min, after which the cooling bath was removed. The reaction mixture was stirred for 24 h, then quenched with 200 mL water, followed by dilution with 200 mL MTBE and 200 mL heptanes. After stirring for 10 min, the layers were separated, and the aqueous layer was filtered through a celite pad. The pad was rinsed with 50 mL water, and the aqueous filtrate was acidified to pH of 1-2 with 2 M HCl. The suspension was diluted with 200 mL MTBE and 100 mL heptanes, stirred for 5 min, then the solids were collected on a fritted glass funnel and rinsed with heptanes. The solids were dried under reduced pressure overnight at 58° C. to afford 24.4 g (70% yield) of the title compound: 1H-NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 5.55 (s, 2H), 6.21 (d, 1H, J=8.4 Hz), 6.24 (d, 1H, J=15.6 Hz), 7.22 (dd, 1H, J=10.4, 2.4 Hz), 7.28 (dd, 1H, J=8.6, 2.0 Hz), 7.34 (s, 1H), 7.43 (dd, 1H, J=8.6, 2.4 Hz), 7.66 (d, 1H, J=15.6 Hz), 7.67 (d, 1H, J=2.4 Hz), 12.29 (s, 1H).

Workup

  1. customthe internal temperature below 18° C.
  2. customafter which the cooling bath was removed
  3. customquenched with 200 mL water
  4. stirringAfter stirring for 10 min
  5. customthe layers were separated
  6. filtrationthe aqueous layer was filtered through a celite pad
  7. washThe pad was rinsed with 50 mL water
  8. additionThe suspension was diluted with 200 mL MTBE and 100 mL heptanes
  9. stirringstirred for 5 min
  10. customthe solids were collected on a fritted glass funnel
  11. washrinsed with heptanes
  12. customThe solids were dried under reduced pressure overnight at 58° C.

Sources & evidence

ORD record
ord-04beb9b3ac7a40e3a8c1800d0614a137
Source dataset
uspto-grants-2009_08
Patent number
US07579483B2

Reaction notes

Loading…