Sodium Hydroxide → HCID 9936657, compound

HRID 1270412Notes

Reaction equation

HRID 1270412 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(O[C:10]([C@@H:12]1[N:16]2[C:17](=O)[C@@H:18]([CH2:22][C:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[NH:25][CH:24]=3)[NH:19][C:20](=O)[C@H:15]2[CH2:14][CH2:13]1)=[O:11])C.[OH-].[Na+].C(N(C(C)C)CC)(C)C.[F:44][C:45]([F:60])([F:59])[C:46]1[CH:47]=[C:48]([CH:52]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:54]=1)[C:49](Cl)=[O:50]>C1COCC1.C(OCC)(=O)C.O>[F:44][C:45]([F:59])([F:60])[C:46]1[CH:47]=[C:48]([C:49]([N:19]2[C@H:18]([CH2:22][C:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[NH:25][CH:24]=3)[CH2:17][N:16]3[C@@H:12]([CH2:10][OH:11])[CH2:13][CH2:14][C@@H:15]3[CH2:20]2)=[O:50])[CH:52]=[C:53]([C:55]([F:56])([F:57])[F:58])[CH:54]=1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 21226445Aluminium lithium hydrideHCID 69035326HCID 69035326, compound

Product 1

HCID 9936657HCID 9936657, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of lithium aluminium hydride (1.2 g) in THF (50 mL) was added a solution of (3R,6R,8aR)-3-(1H-Indol-3-ylmethyl)-1,4-dioxo-octahydro-pyrrolo[1,2-a]pyrazine-6-carboxylic acid ethyl ester (1.75 g) in THF (50 mL). The resulting mixture was heated under reflux for 3 hours, then a mixture of water (3 mL) and THF (30 mL) was added drop-wise followed by 50% sodium hydroxide (aq, 0.5 mL), and heating under reflux was continued for 2 hours. After cooling to room temperature diisopropylethylamine (4 mL) and 3,5-bis(trifluoromethyl)benzoyl chloride (2.4 mL) were added and stirring was continued overnight. Ethyl acetate was added and the mixture extracted with sodium bicarbonate (5% aq. soln.). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH/NH4OH 95:4.5:0.5) to afford 3,5-bis(trifluoromethyl)phenyl-[(3R,6R,8aR)-6-hydroxymethyl-3-(1H-indol-3-ylmethyl)-hexahydropyrrolo[1,2-a]pyrazin-2-yl]-methanone (1.49 g). MH+ 526; Rf 0.20 (EtOAc) (compound 1).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 3 hours
  3. additionwas added drop-wise
  4. temperatureheating
  5. temperatureunder reflux
  6. additionwere added
  7. waitwas continued overnight
  8. extractionthe mixture extracted with sodium bicarbonate (5% aq. soln.)
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH/NH4OH 95:4.5:0.5)

Sources & evidence

ORD record
ord-4c404539a3d5458fb746335e8a613981
Source dataset
uspto-grants-2007_04
Patent number
US07202238B2

Reaction notes

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