Dimethyl Sulfide → HCID 57640341, compound

HRID 2111900Notes

Reaction equation

HRID 2111900 reaction equation
[CH3:1][CH:2]([CH3:20])[CH2:3][N:4]([C:11]([C:13]1[CH:17]=[C:16]([Cl:18])[S:15][C:14]=1[Cl:19])=O)[CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.B(F)(F)F.CCOCC.S(C)C.CN(CCN(C)C)C>O1CCCC1>[CH3:1][CH:2]([CH3:20])[CH2:3][N:4]([CH2:11][C:13]1[CH:17]=[C:16]([Cl:18])[S:15][C:14]=1[Cl:19])[CH:5]1[CH2:6][CH2:7][NH:8][CH2:9][CH2:10]1

Participants

6

Reactant 4

HCID 1068Dimethyl SulfideHCID 8000Boron trifluoride etherateHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 68575109HCID 68575109, compound

Product 1

HCID 57640341HCID 57640341, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(2-methylpropyl)-N-[(2,5-dichlorothiophen-3-yl)-carbonyl]piperidin-4-amine (0.72 g, 2.14 mmol) in anhydrous tetrahydrofuran (5 ml) is added BF3.Et2O (0.73 g, 5.14 mmol) and the reaction mixture is heated to reflux. While refluxing, BH3.Me2S (1.6 ml, 3.2 mmol) is added and the reaction vented to remove Me2S for 10 minutes. After an additional 2 hrs at reflux, TMEDA (0.75 g, 6.42 mmol) is added and the reaction mixture heated at reflux for 1 hr. The reaction mixture is cooled, and the precipitate is filtered and washed with dichloromethane. The filtrate is concentrated in vacuo. Aliquots of methanol (5 ml) are added to the residue and concentrated. This process is repeated until no more gas evolution is observed. The resulting residue is purified on silica gel (0-100%) 5% 2N NH3 in methanol in dichloromethane to give N-(2-methylpropyl)-N-[(2,5-dichlorothien-3-yl)methyl]piperidin-4-amine (0.19 g, 28%). m/z=321 (M+1); 1H NMR (CD3OD): δ=6.87 (1H, s), 3.65 (2H, s), 3.34-3.30 (2H, m), 2.86-2.78 (2H, m), 2.74-2.63 (1H, m), 2.26 (2H, d), 1.95-1.89 (2H, m), 1.72-1.58 (4H, m), 0.86 (6H, d).

Workup

  1. temperaturethe reaction mixture is heated to reflux
  2. temperatureWhile refluxing
  3. customto remove Me2S for 10 minutes
  4. temperatureAfter an additional 2 hrs at reflux
  5. temperaturethe reaction mixture heated
  6. temperatureat reflux for 1 hr
  7. temperatureThe reaction mixture is cooled
  8. filtrationthe precipitate is filtered
  9. washwashed with dichloromethane
  10. concentrationThe filtrate is concentrated in vacuo
  11. additionAliquots of methanol (5 ml) are added to the residue
  12. concentrationconcentrated
  13. customThe resulting residue is purified on silica gel (0-100%) 5% 2N NH3 in methanol in dichloromethane

Sources & evidence

ORD record
ord-b6301dc51b824b31b4c5e87ecf6e6581
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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