Acetic Acid → 5-Methoxy-3-(N-methylthioethyl-N-propionylamino)chroman

HRID 1464697Notes

Reaction equation

HRID 1464697 reaction equation
C(O)(=O)C.[CH3:5][O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH2:9][C:10](=O)[CH2:11][O:12]2.[CH3:18][S:19][CH2:20][CH2:21][NH2:22].C([BH3-])#N.[Na+].[OH-].[Na+].[C:29](Cl)(=[O:32])[CH2:30][CH3:31].C(N(CC)CC)C>C(O)C.CO.C(Cl)Cl.O>[CH3:5][O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH2:9][CH:10]([N:22]([CH2:21][CH2:20][S:19][CH3:18])[C:29](=[O:32])[CH2:30][CH3:31])[CH2:11][O:12]2

Participants

12

Reactant 7

HCID 176Acetic AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 62324Propionyl chlorideHCID 87697(2-(Methylthio)ethyl)amineHCID 5003444Sodium cyanoborohydrideHCID 117690965-Methoxy-3-Chromanone

Product 1

HCID 147034315-Methoxy-3-(N-methylthioethyl-N-propionylamino)chromanYield 64%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the appropriate amine (400 mg, 2.27 mmol) and acetic acid (400 mg, 6.99 mmol) in absolute ethanol (10 ml) was added 5-methoxy-3-chromanone (250 mg, 1.40 mmol), followed by 2-methylthioethylamine (0.6 ml, 6.41 mmol). The solution was stirred with 4 Å molecular sieve for 1 hour 15 min. MeOH (25 ml) was added to the reaction mixture and sodium cyano-borohydride (1.5 g, 23.6 mmol) dissolved in MeOH (10 ml). The reaction mixture was stirred for 30 min, water was added (50 ml) and pH adjusted with 5% aqueous NaOH to 11. The mixture was extracted with CH2Cl2. The phases were separated and the organic layer washed with water, dried (Na2SO4) and the solvent was evaporated. The crude product was immediately propionylated with propionyl chloride (0.5 ml, 5.72 mmol) in CH2Cl2 (20 ml) containing triethylamine (1 ml, 7.2 mmol). The reaction mixture was stirred for 30 min, washed with aqueous sodium carbonate solution, 1N HCl and water. The organic layer was separated and dried (MgSO4). The solvent was evaporated and the crude product chromatographed (SiO2) with light petroleum-ether (1:1) as eluant yielding 276 mg (64%) of the product as an oil. GC/MS (HP-5970A), m/e=310 (0.2) M+, 162 (100), 161 (54), 163 (50), 192 (22).

Workup

  1. stirringThe reaction mixture was stirred for 30 min
  2. extractionThe mixture was extracted with CH2Cl2
  3. customThe phases were separated
  4. washthe organic layer washed with water
  5. dry with materialdried (Na2SO4)
  6. customthe solvent was evaporated
  7. stirringThe reaction mixture was stirred for 30 min
  8. washwashed with aqueous sodium carbonate solution, 1N HCl and water
  9. customThe organic layer was separated
  10. dry with materialdried (MgSO4)
  11. customThe solvent was evaporated
  12. customthe crude product chromatographed (SiO2) with light petroleum-ether (1:1) as eluant

Sources & evidence

ORD record
ord-59f3d643ac3e4c6396db09774f68a709
Source dataset
uspto-grants-1994_04
Patent number
US05306830

Reaction notes

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