Sodium Bicarbonate → 6-Fluoro-3-[1-(8-methoxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-1H-indole

HRID 411598

Reaction equation

HRID 411598 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([O:23][CH3:24])=[CH:20][CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[F:25][C:26]1[CH:34]=[C:33]2[C:29]([C:30]([C:35]3[CH2:36][CH2:37][NH:38][CH2:39][CH:40]=3)=[CH:31][NH:32]2)=[CH:28][CH:27]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.O1CCCC1>[F:25][C:26]1[CH:34]=[C:33]2[C:29]([C:30]([C:35]3[CH2:36][CH2:37][N:38]([CH2:12][CH:13]4[O:18][C:17]5[C:19]([O:23][CH3:24])=[CH:20][CH:21]=[CH:22][C:16]=5[O:15][CH2:14]4)[CH2:39][CH:40]=3)=[CH:31][NH:32]2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 110530726-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 11792133[(2R)-8-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-yl]methyl 4-methylbenzenesulfonate

Product 1

HCID 102719506-Fluoro-3-[1-(8-methoxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-1H-indole

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

[(2R)-8-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-yl]methyl 4-methylbenzenesulfonate (0.30 g, 0.86 mmole), 6-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.60 g, 2.7 mmole) and sodium bicarbonate (0.80 g) were added to a mixture of dimethylformamide/tetrahydrofuran (1:1 v/v, 20 mL) and the reaction mixture was refluxed under nitrogen for 18 hours. The solvent was evaporated and the residue partitioned between 400 mL each of water and methylene chloride. The layers were separated and the methylene chloride solution was washed with water and saturated aqueous sodium chloride solution, dried over anhydrous potassium carbonate and filtered. The filtrate was evaporated in vacuum and the residue crystallized from chloroform containing 3% methanol, giving 0.23 g (68%) of the (S)-enantiomer of the title compound as an off-white solid, m.p. 184-185° C.

Workup

  1. temperaturethe reaction mixture was refluxed under nitrogen for 18 hours
  2. customThe solvent was evaporated
  3. customthe residue partitioned between 400 mL each of water and methylene chloride
  4. customThe layers were separated
  5. washthe methylene chloride solution was washed with water and saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous potassium carbonate
  7. filtrationfiltered
  8. customThe filtrate was evaporated in vacuum
  9. customthe residue crystallized from chloroform containing 3% methanol

Sources & evidence

ORD record
ord-acc11fd42515437f9500a243b1ae8555
Source dataset
uspto-grants-2003_05
Patent number
US06559169B2

Linked notes

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