L-Proline → N-{[6-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amine

HRID 452411Notes

Reaction equation

HRID 452411 reaction equation
Br[C:2]1[C:3]([F:17])=[CH:4][C:5]2[CH2:10][O:9][CH:8]([CH2:11][NH:12][CH2:13][CH2:14][CH3:15])[O:7][C:6]=2[CH:16]=1.[CH3:18][S:19]([O-:21])=[O:20].[Na+].N1CCC[C@H]1C(O)=O>[Cu](I)I.CS(C)=O>[F:17][C:3]1[C:2]([S:19]([CH3:18])(=[O:21])=[O:20])=[CH:16][C:6]2[O:7][CH:8]([CH2:11][NH:12][CH2:13][CH2:14][CH3:15])[O:9][CH2:10][C:5]=2[CH:4]=1

Participants

6

Reactant 3

HCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 44481630N-[(7-bromo-6-fluoro-4H-1,3-benzodioxin-2-yl)methyl]propan-1-amine

Product 1

HCID 44481631N-{[6-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amineYield 45%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Preparation according to Example 18. N-[(7-bromo-6-fluoro-4H-1,3-benzodioxin-2-yl)methyl]propan-1-amine (0.30 g, 0.99 mmol), sodium methanesulfinate (0.15 g, 1.23 mmol, 85%), copperiodide (19 mg, 0.10 mmol), L-proline (56 mg, 0.49 mmol) and DMSO (6 ml) was heated at 140° C. for 1 h. Purification was made twice by flash column chromatography (ETOAc/MeOH 10:1) and afforded the title compound (135 mg, 45%). The amine was converted into the hydrochloric acid salt and crystallized from EtOH/DEE. M.p. 225° C. 1H-NMR (400 MHz, MeOH): δ 7.34 (1H, d, J 6.0 Hz), δ 7.13 (1H, d, J 9.6 Hz), δ 5.21 (1H, t, J 4.8 Hz), δ 5.02 (2H, dd, J1 45.2 Hz, J2 15.6 Hz), δ 3.23 (3H, s), δ 2.96 (2H, m), δ 2.64 (2H, t, J 7.6 Hz), δ 1.56 (2H, m), δ 0.95 (3H, t, J 7.2 Hz).

Workup

  1. customPreparation
  2. customPurification

Sources & evidence

ORD record
ord-809e7fa63ff043afb1c73bf7a94c27b4
Source dataset
uspto-grants-2013_07
Patent number
US08492372B2

Reaction notes

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