Sulfuric acid magnesium salt (1:1) → 1,5-anhydro-2,4-dideoxy-2-(6-(4-methoxybenzyl)-4,5-dimethyl-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-L-threo-pentitol

HRID 629419Notes

Reaction equation

HRID 629419 reaction equation
[CH:1]([C:3]1[C:12]([CH3:13])=[C:11]([CH3:14])[C:10]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[CH:9][C:4]=1[C:5](OC)=[O:6])=O.[NH2:24][C@@H:25]1[C@@H:30]([OH:31])[CH2:29][CH2:28][O:27][CH2:26]1.S([O-])([O-])(=O)=O.[Mg+2]>C1COCC1>[CH3:23][O:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][C:10]2[CH:9]=[C:4]3[C:3]([CH2:1][N:24]([C@@H:25]4[C@@H:30]([OH:31])[CH2:29][CH2:28][O:27][CH2:26]4)[C:5]3=[O:6])=[C:12]([CH3:13])[C:11]=2[CH3:14])=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 55285677(3S,4S)-3-Aminotetrahydro-2H-pyran-4-OLHCID 118468425Methyl 2-formyl-5-(4-methoxybenzyl)-3,4-dimethylbenzoate

Product 1

HCID 1184681511,5-anhydro-2,4-dideoxy-2-(6-(4-methoxybenzyl)-4,5-dimethyl-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-L-threo-pentitolYield 5.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-formyl-5-(4-methoxybenzyl)-3,4-dimethylbenzoate (13.5 g) in THF (270 mL) were added (3S,4S)-3-aminotetrahydro-2H-pyran-4-ol (5.06 g) and anhydrous magnesium sulfate (9.99 g), and the mixture was stirred at room temperature for 5 hr. The insoluble substance was removed by filtration, and the filtrate was concentrated. The residue was diluted with methanol (220 mL)-THF (250 mL), sodium triacetoxyborohydride (18.3 g) was added thereto, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with ethyl acetate, the mixture was washed with water and saturated brine, and the organic layer was dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure. The resulting solid was washed with ethyl acetate to give the crude title compound (6.4 g). The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.85 g). The crude title compound and the title compound purified by column were combined, and recrystallized from ethanol to give the title compound (6.48 g).

Workup

  1. customThe insoluble substance was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. additionThe residue was diluted with methanol (220 mL)-THF (250 mL), sodium triacetoxyborohydride (18.3 g)
  4. additionwas added
  5. stirringthe mixture was stirred at room temperature for 15 hr
  6. additionThe reaction mixture was diluted with ethyl acetate
  7. washthe mixture was washed with water and saturated brine
  8. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  9. concentrationThe organic layer was concentrated under reduced pressure
  10. washThe resulting solid was washed with ethyl acetate
  11. customto give the crude title compound (6.4 g)
  12. concentrationThe filtrate was concentrated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-024e079b704347a08597a6dc64817fff
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Reaction notes

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