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

HRID 629431Notes

Reaction equation

HRID 629431 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[C:23](=[O:26])[NH:24][CH3:25])[CH2:5][C:6]1[C:7]([CH3:19])=[C:8]([CH3:18])[C:9]([CH:16]=O)=[C:10]([CH:15]=1)[C:11](OC)=[O:12].[NH2:27][C@@H:28]1[C@@H:33]([OH:34])[CH2:32][CH2:31][O:30][CH2:29]1.S([O-])([O-])(=O)=O.[Mg+2]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[C:23](=[O:26])[NH:24][CH3:25])[CH2:5][C:6]1[CH:15]=[C:10]2[C:9]([CH2:16][N:27]([C@@H:28]3[C@@H:33]([OH:34])[CH2:32][CH2:31][O:30][CH2:29]3)[C:11]2=[O:12])=[C:8]([CH3:18])[C:7]=1[CH3:19]

Participants

5

Reactant 3

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 55285677(3S,4S)-3-Aminotetrahydro-2H-pyran-4-OLHCID 118468256Methyl 5-(3-fluoro-4-(methylcarbamoyl)benzyl)-2-formyl-3,4-dimethylbenzoate

Product 1

HCID 1184684171,5-anhydro-2,4-dideoxy-2-(6-(3-fluoro-4-(methylcarbamoyl)benzyl)-4,5-dimethyl-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-L-threo-pentitolYield 37.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-(3-fluoro-4-(methylcarbamoyl)benzyl)-2-formyl-3,4-dimethylbenzoate (0.09 g) in THF (2.00 mL) were added (3S,4S)-3-aminotetrahydro-2H-pyran-4-ol (0.03 g) and anhydrous magnesium sulfate (0.06 g), and the mixture was stirred at room temperature for 5 hr. The reaction mixture was concentrated, and the residue was diluted with methanol (2.00 mL)-THF (2.00 mL). Sodium triacetoxyborohydride (0.11 g) was added thereto, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate) to give the title compound (0.04 g).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with methanol (2.00 mL)-THF (2.00 mL)
  3. additionSodium triacetoxyborohydride (0.11 g) was added
  4. stirringthe mixture was stirred overnight at room temperature
  5. additionThe reaction mixture was diluted with ethyl acetate
  6. washthe mixture was washed with water and saturated brine
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-b98be4e9b0c54aa2b4df1e10453c332c
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Reaction notes

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