Acetonitrile → HCID 67155628, compound

HRID 452455Notes

Reaction equation

HRID 452455 reaction equation
[CH3:1][NH:2][CH2:3][CH:4]1[O:9][C:8]2[CH:10]=[C:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:12]=[CH:13][C:7]=2[CH2:6][O:5]1.[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C(#N)C>CCOC(C)=O>[CH2:18]([N:2]([CH3:1])[CH2:3][CH:4]1[O:9][C:8]2[CH:10]=[C:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:12]=[CH:13][C:7]=2[CH2:6][O:5]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 44481362HCID 44481362, compound

Product 1

HCID 67155628HCID 67155628, compoundYield 63.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

N-methyl-1-[7-(methylsulfonyl)-4H-1,3-benzodioxin-2-yl]methanamine (1.05 g, 4.1 mmol), benzylbromide (0.49 ml, 4.1 mmol), potassium carbonate (0.68 g, 4.9 mmol) and ACN (20 ml) were heated at 50° C. for 12 h. EtOAc was added, the reaction mixture was filtered and concentrated. Purification by flash chromatography (isooctane/EtOAc 1:2) afforded the title compound (0.91 g). 1H-NMR (400 MHz, MeOH): δ 7.38 (1H, dd, J 8.4 Hz, J2 1.6), δ 7.28-7.14 (7H, m), δ 5.17 (1H, t, J 4.0 Hz), δ 4.90 (2H, dd, J 52.0 Hz, J2 19.6 Hz), δ 3.59 (2H, dd, J 18.4 Hz, J2 13.2 Hz), δ 2.99 (3H, s), δ 2.78-2.67 (2H, m), δ 2.29 (3H, s). Chiral separation was performed according to Preparation 16. The flow rate was 30 ml/min. Repeated injections (˜40 mg) every 7-8 min. Totally 25 injections afforded the two different enantiomers. The first eluted peak consisted of (−)-N-benzyl-N-methyl-1-{[7-(methylsulfonyl)-4H-1,3-benzodioxin-2-yl]methanamine (0.37 g, >95% e.e.). The second eluted peak consisted of (+)-N-benzyl-N-methyl-1-{[7-(methylsulfonyl)-4H-1,3-benzodioxin-2-yl]methanamine (0.37 g, >95% e.e.).

Workup

  1. filtrationthe reaction mixture was filtered
  2. concentrationconcentrated
  3. customPurification by flash chromatography (isooctane/EtOAc 1:2)

Sources & evidence

ORD record
ord-c5d4a67418a14b1c9e71b92ff65c26d9
Source dataset
uspto-grants-2013_07
Patent number
US08492372B2

Reaction notes

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