(3S,4S)-3-Aminotetrahydro-2H-pyran-4-OL → 1,5-anhydro-2,4-dideoxy-2-(6-(4-(difluoromethoxy)benzyl)-4,5-dimethyl-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-L-threo-pentitol

HRID 629448Notes

Reaction equation

HRID 629448 reaction equation
[F:1][CH:2]([F:25])[O:3][C:4]1[CH:24]=[CH:23][C:7]([CH2:8][C:9]2[C:10]([CH3:22])=[C:11]([CH3:21])[C:12]([CH:19]=O)=[C:13]([CH:18]=2)[C:14](OC)=[O:15])=[CH:6][CH:5]=1.[NH2:26][C@@H:27]1[C@@H:32]([OH:33])[CH2:31][CH2:30][O:29][CH2:28]1>C1COCC1>[F:1][CH:2]([F:25])[O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:9]2[CH:18]=[C:13]3[C:12]([CH2:19][N:26]([C@@H:27]4[C@@H:32]([OH:33])[CH2:31][CH2:30][O:29][CH2:28]4)[C:14]3=[O:15])=[C:11]([CH3:21])[C:10]=2[CH3:22])=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 55285677(3S,4S)-3-Aminotetrahydro-2H-pyran-4-OLHCID 118468382Methyl 5-(4-(difluoromethoxy)benzyl)-2-formyl-3,4-dimethylbenzoate

Product 1

HCID 1184684231,5-anhydro-2,4-dideoxy-2-(6-(4-(difluoromethoxy)benzyl)-4,5-dimethyl-1-oxo-1,3-dihydro-2H-isoindol-2-yl)-L-threo-pentitolYield 56.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-(4-(difluoromethoxy)benzyl)-2-formyl-3,4-dimethylbenzoate (0.04 g) in THF (2.00 mL) was added (3S,4S)-3-aminotetrahydro-2H-pyran-4-ol (0.01 g) under argon atmosphere, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated, and the residue was diluted with acetic acid (2.00 mL). Sodium triacetoxyborohydride (0.03 g) was added thereto under argon atmosphere, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with saturated aqueous sodium bicarbonate solution, and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.02 g).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with acetic acid (2.00 mL)
  3. additionSodium triacetoxyborohydride (0.03 g) was added
  4. stirringunder argon atmosphere, and the mixture was stirred overnight at room temperature
  5. additionThe reaction mixture was diluted with saturated aqueous sodium bicarbonate solution
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by NH silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e790be11ab30449cad467b62fcb84aa7
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Reaction notes

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