Hydrochloric Acid → HCID 69433569, compound

HRID 1352684Notes

Reaction equation

HRID 1352684 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH:6]2[CH2:5][CH2:4]1.C([Li])CCC.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22](OC)[N:21]=1.Cl>C1COCC1>[OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][N:10]([C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH3:18])[N:21]=3)[CH2:11][CH:6]2[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 803782,6-DimethoxypyridineHCID 12985539(Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanolHCID 178418339Butyllithium

Product 1

HCID 69433569HCID 69433569, compoundYield 37.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

According to the procedure reported by Wynberg (J. Org. Chem. 1993, 58, 5101), a solution 0.50 g (2.9 mmol) of racemic (7RS,9aSR)-7-hydroxymethyl-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine in 10 mL of dry THF at 0° C. was treated with 2.59 mL (6.5 mmol) of n-butyl lithium (2.5 M in hexane). The mixture was kept at 0° C. for 30 min and at room temperature for 1 h, and 0.39 mL (2.94 mmol) of 2,6-dimethoxypyridine was added and the solution refluxed for 16 h. After cooling to room temperature, the mixture was poured into 1 M HCl and washed with toluene (3×). The aqueous layer was basified with 1 M NaOH and extracted with toluene (1×) and ethyl acetate (1×). The combined organic layers were dried (magnesium sulfate), filtered, and evaporated to give a yellow oil. Purification by flash silica gel chromatography with 9:1 chloroform:methanol gave 0.304 g (37%) of (7RS,9aSR)-7-hydroxymethyl-2-(6-methoxypyridin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine.

Workup

  1. temperaturethe solution refluxed for 16 h
  2. washwashed with toluene (3×)
  3. extractionextracted with toluene (1×) and ethyl acetate (1×)
  4. dry with materialThe combined organic layers were dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a yellow oil
  8. customPurification by flash silica gel chromatography with 9:1 chloroform

Sources & evidence

ORD record
ord-6c58d37de6ea443ea119ebab029b6007
Source dataset
uspto-grants-2007_05
Patent number
US07220753B2

Reaction notes

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