Sulfuric Acid → Ammonium Hydroxide

HRID 1352702Notes

Reaction equation

HRID 1352702 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[N:7]1[CH2:12][CH2:11][N:10]2[CH2:13][CH:14]([CH2:17][C:18]#N)[CH2:15][CH2:16][CH:9]2[CH2:8]1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([Mg]Br)=[CH:23][CH:22]=1.S(=O)(=O)(O)[OH:30].C(=O)([O-])[O-:35].[Na+].[Na+]>C1COCC1.C(OCC)C.O>[OH-:30].[NH4+:1].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:18](=[O:35])[CH2:17][CH:14]2[CH2:13][N:10]3[CH2:11][CH2:12][N:7]([C:2]4[N:1]=[CH:6][CH:5]=[CH:4][N:3]=4)[CH2:8][CH:9]3[CH2:16][CH2:15]2)=[CH:23][CH:22]=1

Participants

9

Reactant 4

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 69430029HCID 69430029, compoundHCID 178418676HCID 178418676, compound

Product 2

HCID 14923Ammonium HydroxideHCID 20654264HCID 20654264, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.200 g (0.78 mmol) of [(7SR,9aSR)-2-(pyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazin-7-yl]acetonitrile in 4 mL of dry THF was treated with 4.3 mg (0.03 mmol) of cuprous bromide and 0.85 mL (0.85 mmol) of 4-fluorophenyl magnesium bromide (1M in THF), and the mixture was refluxed for 48 h. The mixture was cooled to room temperature, 0.75 mL of water was added carefully followed by 3.5 mL of 15% sulfuric acid. The mixture was refluxed for 24 h. The reaction was cooled to room temperature, and 10% sodium carbonate solution was added until gas evolution ceased. Ethyl ether (10 mL) was added, the layers were separated, and the aqueous phase was extracted with ethyl ether (2×10 mL). The combined organics were dried (sodium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with ethyl acetate:hexane:methanol:conc. ammonium hydroxide (1:1:0.01:0.01) gave 30 mg of the title compound. 13C NMR (CDCl3): d 25.1, 28.3, 29.9, 40.2, 43.7, 49.1, 54.8, 59.1, 61.1, 109.7, 115.4, 115.7, 130.8, 130.9, 134.0, 157.7, 161.5, 164.0, 167.4. HRMS calcd for C20H23FN4O: 354.1856, found: 354.1847.

Workup

  1. temperaturethe mixture was refluxed for 48 h
  2. temperatureThe mixture was refluxed for 24 h
  3. temperatureThe reaction was cooled to room temperature
  4. customthe layers were separated
  5. extractionthe aqueous phase was extracted with ethyl ether (2×10 mL)
  6. dry with materialThe combined organics were dried (sodium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by flash silica gel chromatography with ethyl acetate

Sources & evidence

ORD record
ord-bd6420578aed4c91ae66329b8fadd431
Source dataset
uspto-grants-2007_05
Patent number
US07220753B2

Reaction notes

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