L-Proline → 1-[5-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]-N-methylmethanamine

HRID 452409Notes

Reaction equation

HRID 452409 reaction equation
Br[C:2]1[CH:3]=[C:4]([F:15])[C:5]2[CH2:10][O:9][CH:8]([CH2:11][NH:12][CH3:13])[O:7][C:6]=2[CH:14]=1.[CH3:16][S:17]([O-:19])=[O:18].[Na+].N1CCC[C@H]1C(O)=O>[Cu](I)I.CS(C)=O>[F:15][C:4]1[C:5]2[CH2:10][O:9][CH:8]([CH2:11][NH:12][CH3:13])[O:7][C:6]=2[CH:14]=[C:2]([S:17]([CH3:16])(=[O:19])=[O:18])[CH:3]=1

Participants

6

Reactant 3

HCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 67155865(7-Bromo-5-fluoro-4H-1,3-benzodioxin-2-YL)-N-methylmethanamine

Product 1

HCID 444816291-[5-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]-N-methylmethanamineYield 10%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Preparation according to Example 17 with a small alteration, no base used. 1-(7-bromo-5-fluoro-4H-1,3-benzodioxin-2-yl)-N-methylmethanamine (0.33 g, 1.2 mmol), sodium methanesulfinate (0.18 g, 1.49 mmol, 85%), copperiodide (23 mg, 0.12 mmol), L-proline (69 mg, 0.60 mmol) and DMSO (6.0 ml) was heated at 140° C. for 45 min. Purification by flash column chromatography (EtOAc/MeOH 4:1) afforded the title compound (30 mg, 10%). The amine was converted into the hydrochloric acid salt and crystallized from MeOH/EtOH/DEE. The crystals were washed thoroughly with DEE. M.p. 234° C. 1H-NMR (400 MHz, MeOH): δ 7.28 (2H, m), δ 5.26 (1H, t, J 4.8 Hz), δ 5.05 (2H, dd, J1 20.4 Hz, J2 16.0 Hz), δ 3.13 (3H, s), δ 2.95 (2H, m), δ 2.47 (3H, s).

Workup

  1. customPreparation
  2. customPurification by flash column chromatography (EtOAc/MeOH 4:1)

Sources & evidence

ORD record
ord-6aa5cef8463f4bb8b9fb44c34c6134cb
Source dataset
uspto-grants-2013_07
Patent number
US08492372B2

Reaction notes

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