Hydrochloric Acid → (7RS,9aSR)-7-hydroxymethyl-2-(2-cyano4-fluorophenyl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine

HRID 1977025Notes

Reaction equation

HRID 1977025 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.F[C:14]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:15]=1[C:16]#[N:17].Cl>CS(C)=O>[OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][N:10]([C:14]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:15]=3[C:16]#[N:17])[CH2:11][CH:6]2[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 1235582,5-DifluorobenzonitrileHCID 12985539(Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanol

Product 1

HCID 69432665(7RS,9aSR)-7-hydroxymethyl-2-(2-cyano4-fluorophenyl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazineYield 28.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 1.05 g (6.17 mmol) of (7RS,9aSR)-7-hydroxymethyl-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (U.S. Pat. No. 5,326,874) and 1.29 g (9.25 mmol) of 2,5-difluorobenzonitrile in 20 mL of DMSO was heated at 100° C. for 16 h. The mixture was cooled to room temperature, acidified with 1M HCl, washed with ether (3×), made basic with conc. ammonium hydroxide, and extracted with ethyl acetate (3×). The combined organic layers were washed with water (3×), dried (magnesium sulfate), filtered and evaporated. Purification by silica gel MPLC with 90:10 chloroform:methanol gave 0.51 g of (7RS,9aSR)-7-hydroxymethyl-2-(2-cyano-4-fluorophenyl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine.

Workup

  1. washwashed with ether (3×)
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with water (3×)
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by silica gel MPLC with 90:10 chloroform

Sources & evidence

ORD record
ord-f7c1d23837cf4ffe80d87f6e9937e9cf
Source dataset
uspto-grants-2001_05
Patent number
US06231833B1

Reaction notes

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