HCID 22874537, compound → HCID 22874538, compound

HRID 263710Notes

Reaction equation

HRID 263710 reaction equation
C([O:8][C:9]([CH2:11][C@H:12]([NH:28][C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])[C:13]([N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][C@H:16]1[C:24]([O:26][CH3:27])=[O:25])=[O:14])=[O:10])C1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[C:9]([CH2:11][C@H:12]([NH:28][C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])[C:13]([N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][C@H:16]1[C:24]([O:26][CH3:27])=[O:25])=[O:14])([OH:10])=[O:8]

Participants

4

Reactant 1

HCID 22874537HCID 22874537, compound

Product 1

HCID 22874538HCID 22874538, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 1-[(S)-3-(benzyloxycarbonyl)-2-(trifluoroacetylamino)propionyl]-2,3-dihydroindole-2-(S)-carboxylate (30.1 g, 63 mmol) in ethyl acetate (450 mL) is hydrogenated on the Parr apparatus at 50 psi in the presence of 10% palladium on carbon (15 g) for 105 minutes. The catalyst is filtered off and the filtrate is concentrated under reduced pressure. The residue is partitioned between ether (350 mL) and water (100 mL). The organic layer is washed successively with 1N HCl (100 mL) and water (2×100 mL), then dried over anhydrous sodium sulfate and filtered. The filtrated is decolorized with charcoal, then filtered through a thin layer of silica gel (flash grade). The product is eluted with ether (200 mL). The solvent is evaporated under reduced pressure and the residue crystallized from ether-hexane (1:1). The white crystals are collected and dried under high vacuum for 1 hour at 40° C., then for 18 hours at room temperature to yield methyl 1-[(S)-3-carboxy-2-(trifluoroacetylamino)-propionyl]-2,3-dihydroindole-2-(S)-carboxylate, m.p. 157°-158° C.; [α]D =-188.76 (CHCl3, c 1.1).

Workup

  1. filtrationThe catalyst is filtered off
  2. concentrationthe filtrate is concentrated under reduced pressure
  3. customThe residue is partitioned between ether (350 mL) and water (100 mL)
  4. washThe organic layer is washed successively with 1N HCl (100 mL) and water (2×100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. filtrationfiltered through a thin layer of silica gel (flash grade)
  8. washThe product is eluted with ether (200 mL)
  9. customThe solvent is evaporated under reduced pressure
  10. customthe residue crystallized from ether-hexane (1:1)
  11. customThe white crystals are collected
  12. customdried under high vacuum for 1 hour at 40° C.

Sources & evidence

ORD record
ord-8edb7ac6f2394d5c9119040a10e89c14
Source dataset
uspto-grants-1997_07
Patent number
US05644055

Reaction notes

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