Potassium Carbonate → HCID 9845105, compound

HRID 1789980Notes

Reaction equation

HRID 1789980 reaction equation
[CH3:1][C:2]1([CH3:19])[N:11]2[CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH:13]3[C:9]3[C:10]2=[C:5]([CH:6]=[CH:7][CH:8]=3)[N:4]([CH3:18])[CH2:3]1.Cl[CH2:21][CH2:22][CH2:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)=[O:25].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[F:32][C:29]1[CH:28]=[CH:27][C:26]([C:24](=[O:25])[CH2:23][CH2:22][CH2:21][N:15]2[CH2:16][CH2:17][CH:12]3[N:11]4[C:10]5[C:9]([CH:13]3[CH2:14]2)=[CH:8][CH:7]=[CH:6][C:5]=5[N:4]([CH3:18])[CH2:3][C:2]4([CH3:19])[CH3:1])=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 197503-(4-Fluorobenzoyl)propyl chlorideHCID 10149253HCID 10149253, compound

Product 1

HCID 9845105HCID 9845105, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1,1,3-trimethyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline (from Example 283) (82 mg, 0.32 mmol) in dioxane (10 mL) at rt was added 4-chloro-1-(4-fluorophenyl)butan-1-one (83 mg, 0.42 mmol), K2CO3 (100 mg), KI (30 mg) and stirred at 25° C. for 24 hours. The solution was diluted with water (30 mL) and extracted with EtOAc (2×30 mL). The combined extracts were dried over magnesium sulfate, concentrated, and purified by flash chromatography to afford the title compound (58 mg, 43%). MS [M+H]+ 422. 1H NMR (CDCl3, 300 MHz): δ 8.01 (m, 2H), 7.15 (t, 2H, J=7.7 Hz), 6.65 (t, 1H, J=7.7 Hz), 6.51 (d, 1H, J=7.0 Hz), 6.43 (d, 1H, J=7.0 Hz), 3.63 (m, 1H), 3.25 (d, 1H, J=11 Hz), 3.09 (m, 2H), 2.89 (s, 3H), 2.63 (m, 2H), 2.25 (m, 2H), 2.17 (m, 2H), 1.31 (s, 3H), 1.12 (s, 3H) ppm. This racemate was then separated into its corresponding enantiomers by HPLC utilizing a Chiralcel AD column with 50% Ethanol/Methanol solvent system.

Workup

  1. extractionextracted with EtOAc (2×30 mL)
  2. dry with materialThe combined extracts were dried over magnesium sulfate
  3. concentrationconcentrated
  4. custompurified by flash chromatography

Sources & evidence

ORD record
ord-38abd261a10a4ad5a41e06e9071cc622
Source dataset
uspto-grants-2006_07
Patent number
US07071186B2

Reaction notes

Loading…