Potassium Sodium Tartrate → 1-Oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carbaldehyde

HRID 77361Notes

Reaction equation

HRID 77361 reaction equation
[O:1]=[C:2]1[NH:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[CH:5][N:4]2[C:18]([C:21]#N)=[CH:19][CH:20]=[C:3]12.[H-].C([Al+]CC(C)C)C(C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=[O:36].[Na+].[K+]>C(Cl)Cl>[O:1]=[C:2]1[NH:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:15])([F:17])[F:16])=[CH:10][CH:9]=2)=[CH:5][N:4]2[C:18]([CH:21]=[O:36])=[CH:19][CH:20]=[C:3]12

Participants

5

Reactant 3

HCID 9357Potassium Sodium TartrateHCID 21225700Diisobutylaluminumhydride2×HCID 727149431-Oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carbonitrile

Product 1

HCID 867066601-Oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carbaldehydeYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-75 °C

Procedure

A mixture of 1-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carbonitrile (Example 2) (55 mg, 0.18 mmol) in methylene chloride (1 mL) cooled −75° C. was treated dropwise with 1M diisobutylaluminum hydride in methylene chloride (275 μL, 0.27 mmol). The reaction was stirred at −75° C. for 1.5 h. At this time, the reaction was treated with additional 1M diisobutylaluminum hydride in methylene chloride (0.1 mL, 0.1 mmol) and allowed to stir at −75° C. for an additional 1 h. At this time, the reaction was treated with a solution of Rochelle's salt, and the mixture was allowed to warm up to room temperature where it stirred overnight. At this time, the resulting suspension was absorbed onto silica gel. Flash chromatography (4 g silica column, 0-50% ethyl acetate/hexanes) afforded 1-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-pyrrolo[1,2-a]pyrazine-6-carbaldehyde (22 mg, 40%) as light yellow solid. 1H NMR (acetone-d6) δ ppm 10.02 (s, 1H), 8.11 (d, J=1.5 Hz, 1H), 8.03 (d, J=8.0 Hz, 2H), 7.89 (d, J=8.5 Hz, 2H), 7.85 (s, 1H), 7.42 (s, 1H). LC-MS calcd. for C15H10F3N2O2 [(M+H)+] 307, obsd. 306.8.

Workup

  1. stirringto stir at −75° C. for an additional 1 h
  2. temperatureto warm up to room temperature where it
  3. stirringstirred overnight
  4. customAt this time, the resulting suspension was absorbed onto silica gel

Sources & evidence

ORD record
ord-7a36bf40573e4080b19c075ef0998172
Source dataset
uspto-grants-2014_09
Patent number
US08841299B2

Reaction notes

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