Sodium Sulfate → 2-(4-(3-chlorobenzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methyl ethanamine

HRID 1404140Notes

Reaction equation

HRID 1404140 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][O:6][C:7]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9]([CH2:18][C:19]([NH:21][CH3:22])=O)=[CH:10][N:11]2[CH3:17].[H-].[Al+3].[Li+].[H-].[H-].[H-].[Al+3].[Cl-].[Cl-].[Cl-].[O-]S([O-])(=O)=O.[Na+].[Na+]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][O:6][C:7]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9]([CH2:18][CH2:19][NH:21][CH3:22])=[CH:10][N:11]2[CH3:17]

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 583039872-(4-(3-chlorobenzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methyl acetamide

Product 1

HCID 509973972-(4-(3-chlorobenzyloxy)-5-fluoro-1-methyl-1H-indol-3-yl)-N-methyl ethanamineYield 23%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 33-7 (50 mg, 0.139 mmol) in THF (10 mL) was added dropwise into the solution of lithium aluminum hydride (19 mg, 0.417 mmol) and AlCl3 (41 mg, 0.381 mmol) in THF (10 mL). The mixture was stirred at room temperature for 1 h. Na2SO4.10 H2O was added to quench the reaction. The solid was filtered off and washed with ethyl acetate (20 mL). The organic solvent was washed with brine (3×30 mL), dried over MgSO4, filtered and evaporated. The resulting residue was purified by preparative HPLC (acid condition, water/CH3CN, 30-35% CH3CN in 7.5 min, RT=6.5 min) to give 33-8 (11 mg, 23%) as a yellow solid. 1H-NMR (400 MHz, CDCl3): δ (ppm) 8.80-8.60 (brs, 1H), 7.47 (s, 1H), 7.34 (s, 2H), 7.28 (s, 1H), 7.02-6.99 (m, 1H), 6.92-6.89 (m, 2H), 5.25 (s, 2H), 3.66 (s, 3H), 3.13-3.05 (m, 4H), 2.45 (s, 3H). LRMS: calc and found: 347.1 [M+1].

Workup

  1. customto quench
  2. customthe reaction
  3. filtrationThe solid was filtered off
  4. washwashed with ethyl acetate (20 mL)
  5. washThe organic solvent was washed with brine (3×30 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe resulting residue was purified by preparative HPLC (acid condition, water/CH3CN, 30-35% CH3CN in 7.5 min, RT=6.5 min)

Sources & evidence

ORD record
ord-acc38da7f7b04094bdc1b47b3c43c1d0
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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