Sodium hydride → 2-Dimethylamino-5-fluoro-6-methoxybenzo[b]thiophen-3-yl 4-[2-(1-Pyrrolidinyl)ethoxy]phenyl Ketone

HRID 1387046Notes

Reaction equation

HRID 1387046 reaction equation
[N+]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:12]2[C:13]3[CH:23]=[C:22]([F:24])[C:21]([O:25][CH3:26])=[CH:20][C:14]=3[S:15][C:16]=2[N:17]([CH3:19])[CH3:18])=[O:11])=[CH:6][CH:5]=1)([O-])=O.[H-].[Na+].[OH:29][CH2:30][CH2:31][N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1>CN(C=O)C>[N:32]1([CH2:31][CH2:30][O:29][C:4]2[CH:5]=[CH:6][C:7]([C:10]([C:12]3[C:13]4[CH:23]=[C:22]([F:24])[C:21]([O:25][CH3:26])=[CH:20][C:14]=4[S:15][C:16]=3[N:17]([CH3:19])[CH3:18])=[O:11])=[CH:8][CH:9]=2)[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 762881-PyrrolidineethanolHCID 211828752-Dimethylamino-5-fluoro-6-methoxybenzo[b]thiophene-3-yl 4-Nitrophenyl Ketone

Product 1

HCID 211827452-Dimethylamino-5-fluoro-6-methoxybenzo[b]thiophen-3-yl 4-[2-(1-Pyrrolidinyl)ethoxy]phenyl KetoneYield 220.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 2.0 g (5.34 mmol) of 2-dimethylamino-5-fluoro-6-methoxybenzo[b]thiophene-3-yl 4-nitrophenyl ketone (Part C) and 1.4 g (60% dispersion in mineral oil; 35.0 mmol; washed with hexanes) of NaH in 60 mL of DMF was treated with a solution of 3.75 mL (32.1 mmol) of 1-(2-hydroxyethyl)pyrrolidine in 10 mL of DMF in such rate to control the effervescence. After complete addition, the reaction was stirred at room temperature for 1 h and was quenched by the careful addition of 5 mL of MeOH. The mixture was diluted with 200 mL of EtOAc and was poured into 200 mL of H2O. The two layers were separated and the organic phase was washed with H2O (2×100 mL) and brine (100 mL). The organic phase was dried over K2CO3, filtered, and concentrated in vacuo to give 5.21 g of an amber oil. Purification by flash chromatography (SiO2; gradient of 2% then 5% MeOH in CH2Cl2) afforded 2.10 g (4.74 mmol; 89%) of the title compound as a bright yellow oil.

Workup

  1. additionAfter complete addition
  2. customwas quenched by the careful addition of 5 mL of MeOH
  3. additionThe mixture was diluted with 200 mL of EtOAc
  4. additionwas poured into 200 mL of H2O
  5. customThe two layers were separated
  6. washthe organic phase was washed with H2O (2×100 mL) and brine (100 mL)
  7. dry with materialThe organic phase was dried over K2CO3
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-44eb88969c50465992e6df168efcc510
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

Loading…