Acetone → HCID 86652424, compound

HRID 1261853Notes

Reaction equation

HRID 1261853 reaction equation
[Na].[CH2:2]([O:9][C:10]([N:12]1[C@@H:17]([CH3:18])[C:16](=[O:19])[N:15]2[CH:20]([CH2:23][CH:24]=C)[CH2:21][CH2:22][C@H:14]2[CH2:13]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CC(C)=[O:28]>O.[Os](=O)(=O)(=O)=O>[CH2:2]([O:9][C:10]([N:12]1[C@@H:17]([CH3:18])[C:16](=[O:19])[N:15]2[CH:20]([CH2:23][CH:24]=[O:28])[CH2:21][CH2:22][C@H:14]2[CH2:13]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 180AcetoneHCID 5360545SodiumHCID 67093153HCID 67093153, compound

Product 1

HCID 86652424HCID 86652424, compound

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent

Procedure

Sodium periodiate (206 mg, 0.96 mmol) and osmium tetroxide solution (2.5% in tert-butyl alcohol, 33 μL, 3.3 μmol) were added at 0° C. to a suspension of (3S,8aS)-6-allyl-3-methyl-4-oxo-hexahydro-pyrrolo[1,2-a]pyrazine-2-carboxylic acid benzyl ester (110 mg, 0.33 mmol) in acetone (1 mL) and water (1 mL). After removal of the ice bath the reaction mixture was stirred for 3 h at room temperature, then partitioned between EtOAc and water. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to furnish (3S,8aS)-3-methyl-4-oxo-6-(2-oxo-ethyl)-hexahydro-pyrrolo[1,2-a]pyrazine-2-carboxylic acid benzyl ester [MS: 331.2 (M+H)+]. This was dissolved in DCM (1 mL) and added at room temperature to a suspension of (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride (53 mg, 0.33 mmol), Et3N (33 mg, 0.33 mmol), HOAc (39 mg, 0.66 mmol), and sodium triacetoxyborohydride (77 mg, 0.36 mmol) in DCM (1 mL). After 16 h the reaction mixture was partitioned between EtOAc and 1 M aq. sodium carbonate solution. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; DCM→DCM/MeOH/25% aq. ammonia solution 90:10:0.25) afforded the title compound (88 mg, 62%). Light yellow gum, MS: 442.4 (M+H)+.

Workup

  1. customAfter removal of the ice bath the reaction mixture
  2. custompartitioned between EtOAc and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-89753d4fdd07488292a41b5e2d21c23e
Source dataset
uspto-grants-2013_06
Patent number
US08471004B2

Reaction notes

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