Hydrochloric Acid → (7R,9aS)-7-hydroxymethyl-2-(4-fluoro-2-nitrophenyl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine

HRID 1458772Notes

Reaction equation

HRID 1458772 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:12][N:7]2[CH2:8][CH2:9][NH:10][CH2:11][C@@H:6]2[CH2:5][CH2:4]1.F[C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22].C(=O)([O-])[O-].[Na+].[Na+].Cl>CS(C)=O>[OH:1][CH2:2][C@H:3]1[CH2:12][N:7]2[CH2:8][CH2:9][N:10]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[N+:21]([O-:23])=[O:22])[CH2:11][C@@H:6]2[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 677672,5-DifluoronitrobenzeneHCID 10035034((7R,9AS)-Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanol

Product 1

HCID 54118542(7R,9aS)-7-hydroxymethyl-2-(4-fluoro-2-nitrophenyl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazineYield 78%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 4.38 g (25.8 mmol) of (7R,9aS)-7-hydroxymethyl-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (preparation 1), 4.19 mL (38.7 mmol) of 2,5-difluoronitrobenzene, and 5.46 g (51.5 mmol) of sodium carbonate in 25 mL of DMSO was heated at 95° C. for 16 h. The mixture was cooled to room temperature, acidified with 1M HCl, and washed with ethyl ether (3×). The aqueous layer was 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 flash silica gel chromatography with 90:10 chloroform: methanol gave 6.19 g (78%) of (7R,9aS)-7-hydroxymethyl-2-(4-fluoro-2-nitrophenyl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine.

Workup

  1. washwashed with ethyl 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 flash silica gel chromatography with 90:10 chloroform

Sources & evidence

ORD record
ord-872e3251b46546538a74eba4c3fde69b
Source dataset
uspto-grants-1998_12
Patent number
US05852031

Reaction notes

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