HCID 58928407, compound → HCID 58928364, compound

HRID 851951Notes

Reaction equation

HRID 851951 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[C@@H:14]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([CH3:27])[C:20]=3[CH3:28])[CH2:15][C:16](=O)[CH2:17][C@H:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1COCC1.CO.FC(F)(F)S([O-])(=O)=O.[Zn+2].FC(F)(F)S([O-])(=O)=O>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[C@@H:14]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([CH3:27])[C:20]=3[CH3:28])[CH2:15][CH2:16][CH2:17][C@H:10]2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 1

HCID 58928407HCID 58928407, compound

Product 1

HCID 58928364HCID 58928364, compound

Reagents, catalysts & solvents 3

HCID 104671Zinc trifluoromethanesulfonateCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

(6R,9aS)-2-benzyl-6-(4-methoxy-2,3-dimethylphenyl)-octahydro-pyrido[1,2-a]pyrazin-8-one (9.48 g, 25.0 mmol) is stirred with p-toluenesulfonyl hydrazide (5.60 g, 30.0 mmol, 1.2 eq) in 40 mL anhydrous THF and 200 mL anhydrous MeOH for 20 h at ambient temperature under a nitrogen atmosphere. LC/MS analysis indicates complete conversion to the p-toluenesulfonyl hydrazone. The solution is sparged with argon for 30 min and then treated with 50 mL of a 1.5 M solution of NaCNBH3 in MeOH. Zinc trifluoromethanesulfonate (140 mg, 0.376 mmoles, 1.5%) is added and the solution is heated in a 65° C. oil bath for 5.5 h under an argon balloon. LC/MS analysis indicates consumption of the hydrazone. The mixture is allowed to cool and is quenched with 500 mL of saturated NaHCO3. After stirring vigorously for 30 min, the mixture is extracted with CH2Cl2 (4×200 mL). The combined extracts are dried over Na2SO4, filtered and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with 90%-80% hexanes/EtOAc to yield (6R,9aS)-2-Benzyl-6-(4-methoxy-2,3-dimethylphenyl)-octahydro-pyrido[1,2-a]pyrazine as an oil. LC/MS: 365 (M+1). 1H NMR (400 MHz, CDCl3): 7.34 (1H, d), 7.27 (5H, m), 6.72 (1H, d), 3.79 (3H, s), 3.47 (2H, dd), 3.28 (1H, d), 2.68 (3H, m), 2.28-2.04 (8H, bm), 1.98-1.88 (2H, bm), 1.75 (1H, m), 1.59 (1H, d), 1.50-1.30 (4H, bm).

Workup

  1. customThe solution is sparged with argon for 30 min
  2. additiontreated with 50 mL of a 1.5 M solution of NaCNBH3 in MeOH
  3. customconsumption of the hydrazone
  4. temperatureto cool
  5. customis quenched with 500 mL of saturated NaHCO3
  6. extractionthe mixture is extracted with CH2Cl2 (4×200 mL)
  7. dry with materialThe combined extracts are dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by column chromatography on silica gel eluting with 90%-80% hexanes/EtOAc

Sources & evidence

ORD record
ord-d4bf38d889d542f186441068f0e541ca
Source dataset
uspto-grants-2007_08
Patent number
US07253168B2

Reaction notes

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