Formic Acid → HCID 11323177, compound

HRID 1159012Notes

Reaction equation

HRID 1159012 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5](=[O:16])[N:6]1[CH2:15][CH2:14][NH:13][CH2:12][CH:7]12.[CH:19](O)=O.C=O>O.C(=O)(O)[O-].[Na+]>[CH3:19][N:13]1[CH2:14][CH2:15][N:6]2[C:5](=[O:16])[C:4]3[C:8]([CH:7]2[CH2:12]1)=[CH:9][CH:10]=[CH:11][C:3]=3[C:2]([F:17])([F:1])[F:18]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 11414184HCID 11414184, compound

Product 1

HCID 11323177HCID 11323177, compoundYield 53.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

To a stirring solution of (±)-1,3,4,10b-tetrahydro-7-trifluoromethyl-pyrazino[2,1-a]isoindol-6(2H)-one (60 mg, 0.23 mmol) in water (1 mL) was added formic acid (0.22 mL, 5.9 mmol) and formaldehyde (190 mg, 2.3 mmol; 37% sol. in water). The reaction flask was sealed with a rubber septum (no nitrogen inlet) and warmed to 60° C. The reaction was maintained at this temperature for 24 h and was then cooled. The reaction was then diluted with saturated aqueous sodium bicarbonate, washed with ethyl acetate (3×50 mL), and the combined organic layers were dried over sodium sulfate, filtered, an concentrated. The resulting residue was purified by radial chromatography (2% ammonium hydroxide in 8% methanol in dichloromethane) to afford the desired product (33 mg, 52%) as a pale yellow residue.

Workup

  1. customThe reaction flask was sealed with a rubber septum (no nitrogen inlet)
  2. temperatureThe reaction was maintained at this temperature for 24 h
  3. temperaturewas then cooled
  4. washwashed with ethyl acetate (3×50 mL)
  5. dry with materialthe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. customThe resulting residue was purified by radial chromatography (2% ammonium hydroxide in 8% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0b036f90535c4c1baec5b85fb7116c96
Source dataset
uspto-grants-2010_10
Patent number
US07812024B2

Reaction notes

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