Heptane → Ipragliflozin

HRID 420432Notes

Reaction equation

HRID 420432 reaction equation
CC1C(C)=C(C)C(C)=C(C)C=1.CCCCCCC.B(Cl)(Cl)Cl.[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH:25]=[C:24]1[CH2:32][C:33]1[CH:34]=[C:35]([C@@H:40]2[O:69][C@H:68]([CH2:70][O:71]CC3C=CC=CC=3)[C@@H:59]([O:60]CC3C=CC=CC=3)[C@H:50]([O:51]CC3C=CC=CC=3)[C@H:41]2[O:42]CC2C=CC=CC=2)[CH:36]=[CH:37][C:38]=1[F:39]>ClCCl.CO>[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH:25]=[C:24]1[CH2:32][C:33]1[CH:34]=[C:35]([C@@H:40]2[O:69][C@H:68]([CH2:70][OH:71])[C@@H:59]([OH:60])[C@H:50]([OH:51])[C@H:41]2[OH:42])[CH:36]=[CH:37][C:38]=1[F:39]

Participants

7

Reactant 4

HCID 8900HeptaneHCID 12784PentamethylbenzeneHCID 25135Boron TrichlorideHCID 59426851HCID 59426851, compound

Product 1

HCID 10453870IpragliflozinYield 83.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Pentamethylbenzene (4.85 g) and a n-heptane solution (16.3 mL) containing 1.0 M of boron trichloride were added to a solution of (1s)-1,5-anhydro-1-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-2,3,4,6-tetra-O-benzyl-D-glucitol (2.5 g) dissolved in dichloromethane (50 mL, cooled to −78° C.) in an argon stream. The mixture was stirred at the same temperature for 2 hours. After the completion of the reaction, methanol (100 mL) was added for decomposition of the excessive reagent, and the solvents were removed by vacuum distillation. The residue was purified by silica gel column chromatography (chloroform-methanol). The obtained residue was suspended in a mixed solvent of ethanol and water and was refluxed with heating to dissolve. The resulting solution was slowly cooled to room temperature for recrystallization. The obtained crystal was collected by filtration and then dried under vacuum and heating to obtain (1S)-1,5-anhydro-1-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-D-glucitol (known compound A) (1.1 g) as a white crystal. The differential scanning calorimetry analysis chart (DSC analysis chart) of the known compound A obtained is shown in FIG. 1, and its X-ray powder diffraction chart is shown in FIG. 2.

Workup

  1. additionwas added for decomposition of the excessive reagent
  2. customthe solvents were removed by vacuum distillation
  3. customThe residue was purified by silica gel column chromatography (chloroform-methanol)
  4. temperaturewas refluxed
  5. temperaturewith heating to dissolve
  6. filtrationThe obtained crystal was collected by filtration
  7. customdried under vacuum
  8. temperatureheating

Sources & evidence

ORD record
ord-57e7ff9611bd474b9c2e1e18c2b15fcc
Source dataset
uspto-grants-2012_01
Patent number
US08097592B2

Reaction notes

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