Sodium Bicarbonate → 3-(1-{[8-Fluoro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl}-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

HRID 1823841Notes

Reaction equation

HRID 1823841 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:18][C:17]3[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[NH:24]1[CH2:29][CH:28]=[C:27]([C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[NH:32][CH:31]=2)[CH2:26][CH2:25]1.C(=O)(O)[O-].[Na+]>CN(C)C=O.O1CCCC1>[F:23][C:19]1[C:17]2[O:18][CH:13]([CH2:12][N:24]3[CH2:25][CH:26]=[C:27]([C:30]4[C:38]5[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=5)[NH:32][CH:31]=4)[CH2:28][CH2:29]3)[CH2:14][O:15][C:16]=2[CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 27610233-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indoleHCID 10759436(2R)-8-Fluoro-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl 4-methylbenzenesulfonate

Product 1

HCID 101556703-(1-{[8-Fluoro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl}-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

[(2R)-8-Fluoro-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl 4-methylbenzenesulfonate (1.2 g, 3.5 mmole) was dissolved in a mixture of dimethylformamide/tetrahydrofuran (1:1 v/v, 30 mL) and 3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (0.60 g, 3.0 mmole) added, followed by the addition of sodium bicarbonate (0.60 g, 7.1 mmole) and the mixture refluxed under nitrogen for 18 hours. The solvent was evaporated in vacuum, and the residue partitioned between 400 mL each of methylene chloride and water. The organic phase was dried over magnesium sulfate and filtered. The filtrate was evaporated and the residue chromatographed on silica gel using 4% methanol in chloroform as eluant. The product fractions were combined and concentrated in vacuum to give 0.20 g (16%) of the (S)-enantiomer of the title compound as a yellow solid, m.p. 174–177° C.

Workup

  1. additionadded
  2. temperaturethe mixture refluxed under nitrogen for 18 hours
  3. customThe solvent was evaporated in vacuum
  4. customthe residue partitioned between 400 mL each of methylene chloride and water
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. customThe filtrate was evaporated
  8. customthe residue chromatographed on silica gel using 4% methanol in chloroform as eluant
  9. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-3160548934cb42aba9d0aa118e2a974b
Source dataset
uspto-grants-2006_05
Patent number
US07041683B2

Reaction notes

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