Hydrochloric Acid → HCID 22940601, compound

HRID 1458778Notes

Reaction equation

HRID 1458778 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].[C:13]([N:20]1[CH2:25][CH2:24][N:23]2[CH2:26][C@H:27]([CH2:30]OS(C)(=O)=O)[CH2:28][CH2:29][C@H:22]2[CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].Cl>CN(C=O)C.O>[C:13]([N:20]1[CH2:25][CH2:24][N:23]2[CH2:26][C@H:27]([CH2:30][N:7]3[C:8]4[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=4)[CH:5]=[CH:6]3)[CH2:28][CH2:29][C@H:22]2[CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 678615-FluoroindoleHCID 22940602HCID 22940602, compound

Product 1

HCID 22940601HCID 22940601, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 8.41 g (62 mmol) of 5-fluoroindole in 250 mL of DMF was treated with 2.46 g (62 mmol) of sodium hydride (60% oil dispersion) and the mixture stirred at 50° C. for 1.5 h. Heating was stopped temporarily, 7.73 g (22.2 mmol) of (7R,9aS)-2-BOC-7-(methanesulfonyloxy)methyl-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine in 250 mL of DMF was added, and the mixture stirred at 100° C. for 2 h. The mixture was cooled to room temperature, diluted with water, acidified to pH 2 with 6M hydrochloric acid, and washed with ethyl acetate. The aqueous phase was basified to pH 12 with conc. ammonium hydroxide and extracted with ethyl acetate (3×). The combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with ethyl acetate gave 3.09 g (36%) of (7R,9aS)-2-BOC-7-(5-fluoroindol-1-yl)methyl-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine.

Workup

  1. temperatureHeating
  2. stirringthe mixture stirred at 100° C. for 2 h
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with ethyl acetate
  5. extractionextracted with ethyl acetate (3×)
  6. dry with materialThe combined organic phase was dried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by flash silica gel chromatography with ethyl acetate

Sources & evidence

ORD record
ord-fe3a731af9234abda91387228c32e8ca
Source dataset
uspto-grants-1998_12
Patent number
US05852031

Reaction notes

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