Hydrochloric Acid → HCID 59353073, compound

HRID 1914683Notes

Reaction equation

HRID 1914683 reaction equation
[BH4-].[Na+].[CH3:3][O:4][C:5]1[CH:17]=[CH:16][C:8]([CH:9]=[C:10]2[CH2:15][CH2:14][S:13][CH2:12][CH2:11]2)=[C:7]([N+:18]([O-])=O)[CH:6]=1.Cl>COCCOC.CO>[CH3:3][O:4][C:5]1[CH:17]=[CH:16][C:8]([CH2:9][CH:10]2[CH2:15][CH2:14][S:13][CH2:12][CH2:11]2)=[C:7]([CH:6]=1)[NH2:18]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 4311764Sodium borohydrideHCID 59352990HCID 59352990, compound

Product 1

HCID 59353073HCID 59353073, compoundYield 41.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

Sodium borohydride (63.58 mg; 1.68 mmol; 0.07 eq) is suspended in DME (6.5 mL) at room temperature. Borane-methyl sulfide complex (39.61 mL; 2 M; 79.22 mmol; 3.3 eq) is added dropwise. After 30 min stirring at room temperature, a solution of 4-(4-methoxy-2-nitrobenzylidene)tetrahydro-2H-thiopyran (6.37 g; 24.01 mmol; 1 eq) in DME (100 mL) is added dropwise over 30 min and the orange solution is stirred at room temperature for 30 min then heated up to reflux for 3.5 days. The reaction mixture is quenched with MeOH (40 mL) upon which a yellow-brownish solution is obtained. The solution is stirred at room temperature for 1 h prior to evaporation of the solvent. The oily brownish residue obtained is taken up in MeOH (10 mL) and 5 N HCl (10 mL˜2 eq) is added dropwise while cooling the solution to 0° C. with an ice bath. After addition of ⅔ of the HCl, precipitation starts. The suspension is stored at 4° C. for 30 min. The precipitate is filtered off then washed twice with cold EtOAc (10 mL) to afford 2.39 g (36%) of the title compound as a yellow powder. 1H NMR (DMSO-d6) δ 9.61 (br s, 2H), 7.09-7.06 (m, 1H), 9.95-6.87 (m, 1H), 6.83-6.79 (m, 1H), 3.72 (s, 3H), 2.54-2.47 (m, 6H), 1.87-1.81 (m, 2H), 1.68-1.59 (m, 1H), 1.33-1.20 (m, 2H). HPLC (max plot) 95%; Rt 2.57 min. LC/MS: (ES+): 238.1; (ES−): 236.1.

Workup

  1. additionBorane-methyl sulfide complex (39.61 mL; 2 M; 79.22 mmol; 3.3 eq) is added dropwise
  2. stirringthe orange solution is stirred at room temperature for 30 min
  3. temperaturethen heated up
  4. temperatureto reflux for 3.5 days
  5. customThe reaction mixture is quenched with MeOH (40 mL) upon which a yellow-brownish solution
  6. customis obtained
  7. stirringThe solution is stirred at room temperature for 1 h
  8. customto evaporation of the solvent
  9. customThe oily brownish residue obtained
  10. temperaturewhile cooling the solution to 0° C. with an ice bath
  11. waitThe suspension is stored at 4° C. for 30 min
  12. filtrationThe precipitate is filtered off
  13. washthen washed twice with cold EtOAc (10 mL)

Sources & evidence

ORD record
ord-daf306c7349d4002ba40089d5f9b4c8d
Source dataset
uspto-grants-2013_12
Patent number
US08614215B2

Reaction notes

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